Didier Moukoko

Didier Pourquier

Cécile Genovesio

Simon Thezenas

Patrick Chabrand

Sandrine Roffino

Martine Pithioux
email: martine.pithioux@univ-amu.fr.

GRANULOCYTE-COLONY STIMULATING FACTOR ENHANCES BONE FRACTURE HEALING

Keywords: Three-point-bending test, Fracture healing, Granulocyte-colony stimulating factor, Circulating mesenchymal progenitor cells, Histology

Background

Circulating mesenchymal stem cells contribute to bone repair. Their incorporation in fracture callus is correlated to their bioavailability. In addition, Granulocyte-colony stimulating factor induces the release of vascular and mesenchymal progenitors. We hypothesized that this glycoprotein stimulates fracture healing, and analyzed the effects of its administration at low doses on bone healing. Methods 27 adult male Sprague-Dawley rats underwent mid-femur osteotomy stabilized by centromedullar pinning. In a post (pre) operative group, rats were subcutaneously injected with 5µg/kg per day of Granulocyte-colony stimulating factor for 5 days after (before) surgery. In a control group, rats were injected with saline solution for 5 days immediately after surgery. A radiographic consolidation score was calculated. At day 35, femurs were studied histologically and underwent biomechanical tests. Findings 5 weeks after surgery, mean radiographic scores were significantly higher in the Preop group 7.75 (SD 0.42) and in the Postop group 7.67 (SD 0.52) than in the control group 6.75 (SD 0.69).

Biomechanical tests showed femur stiffness to be more than three times higher in both the Preop 109.24N/mm (SD 51.86) and Postop groups 100.05N/mm (SD 60.24) than in control 32.01N/mm (SD 15.78). Mean maximal failure force was twice as high in the Preop group 68.66 N (SD 27.78) as in the control group 34.21N (SD 11.79). Histological results indicated a later consolidation process in control than in treated groups. Interpretation 3 Granulocyte-colony stimulating factor injections strongly stimulated early femur fracture healing, indicating its potential utility in human clinical situations such as programmed osteotomy and fracture.

Introduction

Fracture consolidation has long been considered a locoregional process involving mesenchymal progenitor cells derived from the tissues damaged by the trauma (local bone marrow, endosteum, bone tissue, periosteum, muscles). Following a series of cellular and molecular event cascades reminiscent of the embryonic stages of skeletal tissue formation, these cell precursors lead to the regeneration of the initially injured tissue. However, the 2000s saw the discovery of circulating osteoprogenitor cells [START_REF] Kuznetsov | Circulating skeletal stem cells[END_REF][START_REF] Labat | On the track of a human circulating mesenchymal stem cell of neural crest origin[END_REF], now known to contribute to the bone formation and repair process [START_REF] Otsuru | Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice[END_REF][START_REF] Otsuru | Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cellderived factor-1 pathway[END_REF]. In physiologic state, these cells represent 1 to 2% of circulating mononuclear cells in adults and nearly 10% in adolescents [START_REF] Eghbali-Fatourechi | Circulating osteoblast-lineage cells in humans[END_REF]. They increase in response to osteogenic requirements: in animals, during an ectopic osteogenesis process, they can transiently rise to 80% of circulating mononuclear cells [START_REF] Otsuru | Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cellderived factor-1 pathway[END_REF]. This cell pool can contribute up to 10% of the osteoblasts present in a fracture consolidation callus [START_REF] Kumagai | Circulating cells with osteogenic potential are physiologically mobilized into the fracture healing site in the parabiotic mice model[END_REF] and as much as 50% of the osteocytes present in an ectopic bone regenerate [START_REF] Otsuru | Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cellderived factor-1 pathway[END_REF].

Intravenous injections of blood-derived osteoprogenitor cells stimulate fracture repair [START_REF] Granero-Molto | Regenerative effects of transplanted mesenchymal stem cells in fracture healing[END_REF][START_REF] Wan | Allogenic peripheral blood derived mesenchymal stem cells (MSCs) enhance bone regeneration in rabbit ulna critical-sized bone defect model[END_REF]. Their rate of incorporation into the callus increases proportionally to their serum bioavailability, until it reaches a plateau. Beyond this value, it remains stable regardless of increases in serum level [START_REF] Granero-Molto | Regenerative effects of transplanted mesenchymal stem cells in fracture healing[END_REF]. On the other hand, endogenous circulating osteoprogenitor cell bioavailability can be transiently boosted by the pharmacological use of bioactive molecules that trigger the mobilization of their medullary precursors, thereby favoring bone repair [START_REF] Kumar | Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect[END_REF][START_REF] Matsumoto | Circulating endothelial/skeletal progenitor cells for bone regeneration and healing[END_REF][START_REF] Toupadakis | Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model[END_REF]. G-CSF is a glycoprotein used in human therapeutics for its ability to mobilize medullary hematopoietic stem cells in systemic circulation. G-CSF also induces the mobilization of vascular stem cells [START_REF] Minamino | Macrophage colonystimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization[END_REF] and mesenchymal stem cells [START_REF] Levesque | Mobilization of bone marrow-derived progenitors[END_REF][START_REF] Tatsumi | Granulocyte-colony stimulating factor increases donor mesenchymal stem cells in bone marrow and their mobilization into peripheral circulation but does not repair dystrophic heart after bone marrow transplantation[END_REF][START_REF] Zhdanov | Mechanism of mobilization of mesenchymal stem cell under the effect of granulocyte colony-stimulating factor[END_REF], both of which are involved, to varying degrees, in skeletal tissue repair. In rats, there was a significant increase in CD34 + progenitor cells after five consecutive injections of G-CSF [START_REF] Herrmann | Five Days Granulocyte Colony-Stimulating Factor Treatment Increases Bone Formation and Reduces Gap Size of a Rat Segmental Bone Defect: A Pilot Study[END_REF]. These cells are capable of differentiating into osteogenic as well as vasculogenic lineages [START_REF] Sidney | Concise review: evidence for CD34 as a common marker for diverse progenitors[END_REF]. Surprisingly, few studies have been published on the use of G-CSF as a skeletal tissue repair or regeneration adjuvant [START_REF] Kaygusuz | The effects of G-CSF and naproxen sodium on the serum TGF-beta1 level and fracture healing in rat tibias[END_REF]Wu et al., 2008). When administered topically, G-CSF improves neovascularization and osteogenesis, which leads to regeneration of both criticalsize bone defects in a rabbit bone resection model [START_REF] Ishida | Bone regeneration properties of granulocyte colony-stimulating factor via neovascularization and osteogenesis[END_REF] and tendon graft in a ligamentoplasty model [START_REF] Sasaki | Enhancement of tendonbone osteointegration of anterior cruciate ligament graft using granulocyte colony-stimulating factor[END_REF]. When administered parenterally, G-CSF counterbalances the negative effects of NSAIDs on bone healing, probably by stimulating osteogenesis [START_REF] Kaygusuz | The effects of G-CSF and naproxen sodium on the serum TGF-beta1 level and fracture healing in rat tibias[END_REF]. In a rabbit femoral osteonecrosis model, the combined use of G-CSF and Stem Cell Factor cause increased osteoblast activity and improve local revascularization, leading to more effective regeneration of the necrotic bone tissue volume (Wu et al., 2008).

To date, only two studies have focused on the effects of parenteral administration of G-CSF on fracture healing [START_REF] Bozlar | Effects of human granulocytecolony stimulating factor on fracture healing in rats[END_REF][START_REF] Herrmann | Five Days Granulocyte Colony-Stimulating Factor Treatment Increases Bone Formation and Reduces Gap Size of a Rat Segmental Bone Defect: A Pilot Study[END_REF], both finding that G-CSF accelerated bone repair in rats. However, the doses used in these studies were respectively 2.5 [START_REF] Bozlar | Effects of human granulocytecolony stimulating factor on fracture healing in rats[END_REF] and 5 times higher [START_REF] Herrmann | Five Days Granulocyte Colony-Stimulating Factor Treatment Increases Bone Formation and Reduces Gap Size of a Rat Segmental Bone Defect: A Pilot Study[END_REF] than the recommended dose in human clinical practice with healthy subjects. In fact, for donors providing peripheral blood stem cells for recipients of hematopoietic stem cell transplants, recombinant human G-CSF is generally recommended at a dose of 10µg/kg per day. Even at this dose, side effects are observed, although when the dose is reduced, the side effects decrease [START_REF] Lambertini | The five "Ws" for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs)[END_REF]. Furthermore, [START_REF] Bozlar | Effects of human granulocytecolony stimulating factor on fracture healing in rats[END_REF] and [START_REF] Herrmann | Five Days Granulocyte Colony-Stimulating Factor Treatment Increases Bone Formation and Reduces Gap Size of a Rat Segmental Bone Defect: A Pilot Study[END_REF] chose to work only on emergency clinical applications (e.g fractures, large defects) and did not consider programmed clinical applications (e.g bone lengthening, tumor removal).

In this work, from a perspective of the eventual therapeutic use of GCSF in humans, we investigated the effects of parenteral administration of a 5µg/kg per day dose of G-CSF on fracture consolidation in rats. We also investigated G-CSF administration pre-surgery vs G-CSF administration post-surgery. Pre-surgery administration mirrors the human clinical situation of a programmed osteotomy, and post-surgery administration mirrors a fracture situation.

Materials and Methods

Twenty-seven male Sprague Dawley rats (OFA), weighing 500g and twelve weeks old at time of surgery were used in the experiment. The animals were fed a standard diet ad libitum. They were housed singly in cages in temperature-controlled rooms (22°C) having a 12h light cycle. All animal protocols were approved by the University of Aix-Marseille institutional animal care and use committee and the French research ministry (authorization number 02572.02), and performed in the conventional animal house of Marseille Medical Faculty (France).

Surgical protocol

The surgical model consisted of right femur mid-diaphyseal osteotomy, immediately osteosynthesized by centromedullary pinning. Under general anesthesia consisting of intraperitoneal Ketamine 75 mg/kg and Medetomidine 0.15 mg/kg and under strictly aseptic conditions, the right femur was exposed via a lateral subperiosteal approach. Medial-diaphyseal osteotomy was performed using piezotome. Retrograde centromedullary pinning (2 mm diameter Kirschner wires) was performed by lateral parapatellar arthrotomy. The muscular fascia was closed with separated resorbable stitches and the skin with slow-absorption continuous stitches.

Postoperative analgesia and prophylactic antibiotic therapy consisted of an injection of Buprenorphine 0.05 mg/kg and subcutaneous Baytril 10 mg/kg peroperatively, then once per day for 3 days. Rats were followed weekly by radio to check that they were healthy.

Experimental groups

Rats were randomized to one of three distinct pharmacological procedures. The "Postoperative" group (Postop) with 9 rats were injected subcutaneously with 5µg/kg per day of G-CSF (FILGRASTIM) for 5 days starting from surgery. The "Preoperative" group (Preop) with 9 rats received identical G-CSF injections for 5 days preoperatively. In the Control group, 9 rats were injected subcutaneously for 5 days with a saline solution, starting immediately after surgery.

One rat died in the control group upon induction of anesthesia. One rat died in the Postop group being found dead one day after surgery. One rat in the Preop group was sacrificed three days after surgery due to splitting of the scar tissue. No locoregional infections or other complications were observed in the other animals. After 35 days of consolidation, the animals were sacrificed by intraperitoneal lethal injections of Sodium Pentobarbital 100 mg/kg.

Radiographic analysis

X-rays of the femurs subjected to surgery were taken immediately postoperatively, then at days 7, 21 under general anesthesia and at day 35 after the sacrifice. A radiographic consolidation score [START_REF] An | Animal models of fracture or osteotomy[END_REF] was calculated from the analysis of the X-rays by two orthopedic surgeons not involved in the study (Table 1) and who analyzed independently each x-ray according to the radiographic scoring system for fracture healing [START_REF] An | Animal models of fracture or osteotomy[END_REF]. The final score assigned to each x-ray was the mean of the scores of the two surgeons.

Table 1: Radiographic scoring system for fracture healing [START_REF] An | Animal models of fracture or osteotomy[END_REF] .

CATEGORY SCORE

Periosteal reaction

• Full (across the defect) 3

• Moderate 2

• Mild 1

• None 0

Bone union

• Union 3

• Moderate bridge (> 50%) 2

• Mild Bridge (< 50%) 1

• Non-union 0

Remodeling

• Full remodeling cortex 2

• Intramedullary canal 1 The fresh material was frozen and stored at -20°C, which does not alter the structure or properties 159 of bone. The samples were slowly thawed at room temperature before preparation and 160 mechanically tested under three-point-bending [START_REF] Turner | Basic biomechanical measurements of bone: a tutorial[END_REF]

•

on a testing device (MTS 161

Instron 5566A, INSTRON© Elancourt, France, 1000N load with an accuracy of 0.19%). We 162 used preconditioning at 1N and subsequently imposed a speed of 0.5mm per min. 10 Force/displacement curves were obtained. Failure force and stiffness of the fracture site were analyzed.

Histological analysis

Six femurs subjected to surgery underwent histological analysis after 35 days of consolidation (2 from control group, 2 from Postop group, 2 from Preop group). The fixation pin was removed and the fracture site was isolated from the femur and fixed in 4% formaldehyde (Merk Millipore) in 0.01M phosphate buffer saline (Sigma-Aldrich) at pH 7.4 for one week. Following fixation, tissue samples were washed with deionized water and were dehydrated through an ethanol gradient of 60%, 80%, 95%, 100% ethanol, each step lasting 48 hours. Samples were cleared in methylcyclohexan (VWR international) for 48h before infiltration and embedding in Methyl methacrylate (MMA) resin (VWR international). Samples then underwent polymerization in a 28°C water bath for 3 days.

After trimming of the blocks, 5µm thick longitudinal sections were obtained using a microtome (Leica© RM 2265, Wetzlar, Germany) equipped with a D-profile tungsten-carbide knife. The sections were transferred to Superfrost Plus slides and stretched with 70% ethanol. Slides were covered with a plastic film, pressed and dried for 2 days. Before staining, MMA was removed from the sections by immersion in three changes of 2-methoxyethylacetate (Merk Millipore) for 20min each, one change of ethanol 70 for 5min, one change of ethanol 40 for 5min, and then rehydrated in two deionized water baths. The sections were stained with toluidine blue and Von Kossa. They were dehydrated and mounted using a resinous mounting medium (Entellan, Merk Millipore).

Statistical analyses

Due to the small size of the groups, we chose to use nonparametric tests. The nonparametric Kruskal-Wallis test was used to compare consolidation scores for the three groups (control, Preop, Postop) at each time point (J7, J21, J35). This same test was used to compare stiffness and failure force values for the three groups, both for the contralateral femurs and for the femurs subjected to surgery. The significance level was set at p<0.05. For the multiple comparisons, we used the Conover-Iman test with a Bonferroni correction. Statistical analysis was performed using XLSTAT software.

Results

Radiographic results

Radiographic consolidation scores for all time points are presented in table 2. In the peripheral callus, asymmetrically distributed around the fracture site, signs of mineralization were visible from 7 days after surgery. At days 7 and 21, a significant difference was observed between the control group and the Postop group alone (p = 0.001 at day 7; p = 0.001 at day 21). At day 35, we observed a significant difference between the control group and the Preop group (p = 0.008) as well as between the control group and the Postop group (p = 0.013). At this date, the osteotomy site remained visible on all femurs, pointing to incomplete remodeling. At each time point, the difference between the two treated groups was not significant (p = 0.094 at day 7; p = 0.046 at day 21; p = 0.806 at day 35).

Mechanical results

5 weeks after surgery, force/displacement curves were obtained for 18 healed femurs from the three experimental groups and for 18 control femurs obtained from their contralateral femurs.

Although the femurs systematically fractured at the level of the bony callus during the 3-point bending tests, two types of failure profile were observed. The control group femurs experienced ductile failure, while the preop and postop groups femurs experienced brittle failure, like the contralateral group femurs (Figure 1). The contralateral femurs did not display any significant difference in mean stiffness (p = 0.24) or in maximum failure force (p = 0.17), irrespective of origin (control, Preop and Postop). Comparing the 3 experimental groups via the Kruskall-Wallis test, we found a significant difference in stiffness (p = 0.011) and maximal failure force (p = 0.024). Concerning stiffness, the multiple comparisons showed that the control group significantly differed both from the Preop group (p= 0.002) and from the Postop group (p = 0.003). Mean callus stiffness was slightly more than three times higher in the Preop 109.24

N

Histological results

In the control group, a fibrous tissue joined the two cortices, while incomplete bony union was

Discussion and conclusion

The concomitant mobilization of angiogenic [START_REF] Minamino | Macrophage colonystimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization[END_REF] and mesenchymal stem cells [START_REF] Wan | Allogenic peripheral blood derived mesenchymal stem cells (MSCs) enhance bone regeneration in rabbit ulna critical-sized bone defect model[END_REF][START_REF] Levesque | Mobilization of bone marrow-derived progenitors[END_REF][START_REF] Tatsumi | Granulocyte-colony stimulating factor increases donor mesenchymal stem cells in bone marrow and their mobilization into peripheral circulation but does not repair dystrophic heart after bone marrow transplantation[END_REF]) by G-CSF suggests its potential contribution to skeletal tissue repair. The purpose of this study was to evaluate the effect of low doses of G-CSF on the consolidation processes in fractures treated by open surgery, mirroring two human clinical situations: programmed osteotomy (Preop group) and fracture (Postop group). Our study showed that a 5µg/kg per day dose is sufficient to stimulate fracture repair processes. Five weeks after surgery, femurs from both treatment groups showed stimulation of osteotomy site consolidation stemming from systemic G-CSF administration. The efficacy of G-CSF in improving bone repair process was previously demonstrated at higher doses in rats, by [START_REF] Herrmann | Five Days Granulocyte Colony-Stimulating Factor Treatment Increases Bone Formation and Reduces Gap Size of a Rat Segmental Bone Defect: A Pilot Study[END_REF] and [START_REF] Bozlar | Effects of human granulocytecolony stimulating factor on fracture healing in rats[END_REF]. In the latter study, in a rat model of tibia fracture, the authors observed a 10-fold increase in callus mechanical strength three weeks after surgery in animals treated with a 25µg/kg per day G-CSF injection. In our study, maximal failure force was twice as high in the Preop group as in the control group, and callus stiffness slightly more than tripled in both G-CSF groups compared to control. Since our mean failure force values obtained on healthy bone were similar to those reported in the literature for rats of the same genetic origin, age and sex (Utvåg et al., 1998a;Utvåg et al., 1998b[START_REF] Utvåg | Influence of flexible nailing in the later phase of fracture healing: strength and mineralization in rat femora[END_REF], methodological issues can be excluded. The difference in mechanical values is probably related to the dose of G-CSF administered. Moreover, we did not observe any impairment of biomechanical behavior in the femurs not subjected to surgery, even though prolonged medullary progenitor cell mobilization is known to lead to deterioration of bone tissue (Wu et al., 2008;[START_REF] Toupadakis | Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling, alters fracture repair[END_REF]. This result is not surprising in view of the short period of injection with G-CSF.

Histological analysis corroborated the biomechanical results. In G-CSF treated animals, we observed the complete replacement of endochondral cartilage by bone trabeculae, evidence that the process of remodeling is underway. In the control group animals, however, we observed the persistence of cartilaginous tissue in the process of ossification, which indicates a later consolidation process than in the treated group. The difference between control group and treated groups in terms of tissue type within the callus probably explains why ductile failure was observed in the control animals' bone and brittle failure in animals treated with G-CSF.

In human clinical practice, G-CSF is administered both to patients with chronic neutropenia or cancer and to donors providing peripheral blood stem cells for recipients of hematopoietic stem cell transplants. In healthy donors, G-CSF is recommended at the dose of 10 µg/kg administered once daily, and although well tolerated, it induces side effects. In a large prospective study, [START_REF] Pulsipher | Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation[END_REF] reported that some rare life-threatening events occurred after G-CSF administration in healthy donors and that no fatalities occurred. In addition, treated donors showed no evidence of increased risk for cancer, autoimmune illness and stroke. The most common adverse event associated with G-CSF administration in healthy donors is bone and musculoskeletal pain [START_REF] Lambertini | The five "Ws" for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs)[END_REF][START_REF] Tigue | Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project[END_REF]. To prevent and treat this pain, nonsteroidal anti-inflammatory agents are commonly used as a first-line treatment, and dose reductions are considered as second-line therapy [START_REF] Lambertini | The five "Ws" for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs)[END_REF]. Thus, with a view to using G-CSF treatment as a fracture repair adjuvant in humans, we chose to test a low dose of G-CSF.

Our therapeutic approach, derived from regenerative medicine, is founded on the welldocumented contribution from circulating progenitor cells to many tissue repair processes.

Stimulation of bone repair processes is related to the increased bioavailability of circulating vascular and mesenchymal progenitor cells at the neo-osteogenesis site [START_REF] Kumar | Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect[END_REF][START_REF] Matsumoto | Circulating endothelial/skeletal progenitor cells for bone regeneration and healing[END_REF][START_REF] Toupadakis | Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model[END_REF][START_REF] Pignolo | Circulating osteogenic cells: implications for injury, repair, and regeneration[END_REF]. Their incorporation into the skeletal tissue repair site contributes to many steps in the cascade of cellular and molecular events of the endochondral osteogenesis processes. During initial stages, these cells modulate the local and systemic inflammatory response [START_REF] Iguchi | Effect of recombinant human granulocyte colony-stimulating factor administration in normal and experimentally infected newborn rats[END_REF] and induce local emission of cytokines such as BMP-2 that initiate bone tissue repair processes [START_REF] Granero-Molto | Regenerative effects of transplanted mesenchymal stem cells in fracture healing[END_REF].

During a later phase, vascular invasion of the cartilage matrix is promoted by angiogenesis and vasculogenesis mechanisms. The latter are supported by the influx and proliferation of circulating angiogenic progenitor cells of medullary origin [START_REF] Matsumoto | Circulating endothelial/skeletal progenitor cells for bone regeneration and healing[END_REF][START_REF] Minamino | Macrophage colonystimulating factor (M-CSF), as well as granulocyte colony-stimulating factor (G-CSF), accelerates neovascularization[END_REF], which depend on their serum level [START_REF] Lee | Mobilization of endothelial progenitor cells in fracture healing and distraction osteogenesis[END_REF]. This neoangiogenesis allows the influx of circulating osteogenic progenitor cells, which are incorporated into the callus undergoing ossification. Their incorporation is also dependent upon their serum level [START_REF] Granero-Molto | Regenerative effects of transplanted mesenchymal stem cells in fracture healing[END_REF]. Now, according to Herrmann et al. (2016), the bioavailability of vascular and osteogenic progenitor cells such as CD34+ significantly increased after five consecutive injections of G-CSF in rats. In addition, in patients with femoral and tibial nonunion, it has been observed radiographically that fracture healing improved when G-CSF-mobilized CD34+ cells were transplanted to non-union sites (Kuroda et al., 2014). Thus, the stimulation of fracture repair by systemically administered G-CSF observed in our study could result from G-CSF-induced medullary mobilization of vascular and mesenchymal progenitor cells in the vascular compartment, leading to increased incorporation at the tissue repair site. Nevertheless, the possibility that G-CSF improves consolidation by other mechanisms cannot be ruled out. [START_REF] Froberg | Changes in serum osteocalcin and bone-specific alkaline phosphatase are associated with bone pain in donors receiving granulocyte-colony-stimulating factor for peripheral blood stem and progenitor cell collection[END_REF] showed that G-CSF induces an increase in blood markers of bone formation such as osteocalcin and bone-specific alkaline phosphatase, which suggests that G-CSF stimulates osteoblastic activity. In addition, the effects of G-CSF could also be related to an increase in some cytokines. In an in vitro model, [START_REF] Kaygusuz | The effects of G-CSF and naproxen sodium on the serum TGF-beta1 level and fracture healing in rat tibias[END_REF] showed that G-CSF, while raising the TGFβ1, has a positive effect on fracture healing and [START_REF] Czekanska | Enhancing inflammatory and chemotactic signals to regulate bone regeneration[END_REF] that stimulation of mesenchymal stem cells by G-CSF results in an upregulation of mRNA expression of BMP2, which is involved in bone formation.

The rate of incorporation of circulating progenitor cells into the fracture callus is time-and dosedependent [START_REF] Granero-Molto | Regenerative effects of transplanted mesenchymal stem cells in fracture healing[END_REF]. These cells can interact both qualitatively and quantitatively at various stages and times in the osteogenesis process [START_REF] Iguchi | Effect of recombinant human granulocyte colony-stimulating factor administration in normal and experimentally infected newborn rats[END_REF][START_REF] Lee | Mobilization of endothelial progenitor cells in fracture healing and distraction osteogenesis[END_REF]. We therefore modulated the bioavailability peak of circulating progenitor cells in order to make it overlap with various times and stages in the bone consolidation process.

We compared two different chronological sequences, one in which the adjuvant treatment preceded the surgical procedure and one in which it followed the surgery. Five weeks after surgery, no significant difference was observed between the Preop and the Postop groups, neither in callus mechanical behavior nor in the biological structure of the regenerated bone at the fracture site. However, mechanical tests are structural analysis, so we have no information about the callus undergoing ossification and its microstructure. Yet the mechanical characteristics of the callus are governed by its morphology, volume and material characteristics, in particular its degree of mineralization and remodeling. Moreover, only the consolidation score of the Postop group differs from that of the control group at days 7 and 21, indicating potential differences in degree of mineralization between the two treated groups. This difference in consolidation score disappears at day 35. This suggests that, despite the similar radiological profile and mechanical behavior of the explants from the two treated groups observed five weeks after surgery, the pharmacological effect of G-CSF may have stimulated different stages in the endochondral ossification process.

During skeletal tissue regeneration, systemic cell mechanisms participate in tissue repair.

Medullary mesenchymal and vascular progenitor cells are mobilized in systemic circulation, then captured at the tissue repair site, where they participate in the various stages of the cellular and molecular events leading to the restoration of injured tissue (Kuroda et al., 2014). G-CSF increases the bioavailability of these circulating progenitor cells. However, we measured neither the kinetics, nor the intensity of blood mobilization of progenitor cells. The correlation between the pharmacological increase in progenitor cell bioavailability and fracture repair stages will be studied in future experimental work. It would be of interest to reevaluate treatment duration and starting time for G-CSF injections relative to the biological phases of the endochondral osteogenesis process. Finally, the stimulation mediated by G-CSF can be considered either in terms of consolidation speed and functional recovery, or in terms of final fracture site strength. In the present study, we chose to study the radiographical, mechanical and histological characteristics of the callus before completion of consolidation and bone remodeling. It would be interesting to follow consolidation callus kinetics to completion. This would reveal whether the final consolidation product is obtained earlier, and whether it is mechanically more efficient in the G-CSF treated groups than in the control group after callus remodeling. Despite its limitations, this study demonstrates that a low-dose, short-term systemic G-CSF adjuvant treatment stimulates fracture repair, indicating its potential utility in human clinical situations such as programmed osteotomy and fracture. The therapeutic modalities of this emerging "regenerative medicine" strategy remain to be determined.

  observed in the periosteal callus (Fig 2a). The latter was composed of centrally located uncalcified and calcified cartilage adjacent to newly woven bone, indicating endochondral ossification (Fig 3a). At the periphery, the periosteal callus consisted of woven and lamellar bone (Fig 2a).No difference was observed between the Preop and the Postop G-CSF-treated groups. Neither of the groups showed any evidence of endochondral ossification. There was complete bony union.The osteotomy gap was filled with anastomosed bone trabeculae in the periosteal region of the callus (Figs2b and 2c) as well as between the cortices (Fig3b). In the internal and periosteal calluses, signs of bone formation and bone resorption indicated that remodeling of regenerated bone was occurring. Bone trabeculae showed on their surface osteoid tissue apposed to rows of osteoblasts and osteoclasts that resorbed bone(Fig 4).

Fig 1 .

 1 Fig 1. Examples of force/displacement curves for femurs from the control, preop, postop

Fig 2 .

 2 Fig 2. Low magnification of the fracture calluses 5 weeks after the osteotomy in control (a),

Fig 3 :

 3 Fig 3: Micrograph of section stained with Von Kossa and counterstained with toluidine blue

Fig 4 :

 4 Fig 4: Micrograph of section stained with toluidine blue from the postop group 5 weeks after

Table 2 : Radiographic score

 2

	Control group	Preop group	Postop group

* Significant by comparison with the control group.

Table 3 .

 3 Mechanical results.

	/mm (SD 51.86) and in the Postop groups 100.05 N/mm (SD 60.24) than in the control group
	32.01 N/mm (SD 15.78).
	Concerning maximal failure force, the multiple comparisons showed that the control group
	significantly differed from the Preop group (p= 0.004) but no difference from the Postop group

was observed (p = 0.053). Mean maximal failure force was twice as high in the Preop group 68.66 N (SD 27.78) as in the control group 34.21N

(SD 11.79)

. No significant difference was Values are Mean (SD). * Significant by comparison with the control group.

Acknowledgements

We are grateful to the staff responsible for the care of the rats in accordance with the French ethics committee. We thank Marylène Lallemand and Flavy Roseren for their excellent technical assistance. We thank Marjorie Sweetko for English language revision of the manuscript.


Foreword: Law in Sudan. An anthropological perspective

This volume is part of a broad comparative program dealing with the anthropology of law in Muslim contexts. Different countries were surveyed, among them Indonesia, Algeria, and Morocco. Although the theme of property was initially central, the program turned out to also focus on two other issues: legal pluralism and law in Islam. In this short preface, I will concentrate on these three themes.

*

Faced with the problems arising from attempts at defining law and from the static approach of the norm, some authors promoted a method founded on practical case studies and the processes of conflict resolution (court room studies). The study of problematic cases has been the focus of American legal realism: how law is practiced, informed by a certain mode of behaviour (behaviourism). Another trend attempted to show how the parties in a litigation conceive the norms and negotiate them during the conflict, how the norms are stated and applied and also neglected or violated. It is therefore the conflict itself which became the focus of attention. These perspectives are fruitful, but do not necessarily constitute the dominant paradigm today, as the theories of legal pluralism currently prevail. Here, the centrality of state law is seen as an ideology. In its most radical formulation, the plurality of laws is considered as the result of the everincreasing gulf between legal practices and textual legal provisions.

In our view, however, the plurality of practices is not an expression of legal pluralism. 1 We actually contend that we must adopt a much more praxeological look at legal phenomena. If we closely examine the fine details of cases, and especially the ways in which people orient to the supposedly many laws and norms, we get a much better picture of what law is and is not for these people. We also get a much better understanding of its plural sources and the non-pluralistic ways of its implementation, and of the many places where laws interfere with each other and the very few places where they remain totally autonomous. Last but not least, norms, laws and legal practices cease to be confounded. Any set of norms is not necessarily law, and law is no more diluted in the all-encompassing and little-analysed category of "social control." Many practices can be characterized as legal practices, and not as parallel social, normative or legal fields. Legal practices are those practices that develop around an object of reference identified by the people as law (which can be state law or any other law recognized as such). In other words, a legal practice is everything that is done in a way in which it would not be done if the law of reference did not exist.

With regards to legal practices of Muslims, very few studies have followed this praxeological path. Our intention was to investigate "into the comprehensibility of society, into the ways in which social life can be understood and described when seen from within by members" (Sharrock and Watson 1988, p. 59). This praxeological approach requires using the "criteria that participants have for determining the salient features of interactional episodes" (Maynard 1984, p. 19), which does not provide an interpretation of people's conduct. Rather, analysis is "based on, and made valid by, the participants' own orientations, characterizations, and exhibited understandings" (ibid.).

*

The program was interested in legal practices related to the questions of land ownership, commercial transactions and family relationships, originating from various places functionally devoted to the resolution of litigations, which can arise in these matters, or to the formulation and registration of documents related to property. These places can be linked to a State (or not), and the laws of reference can also be official or unofficial. Thus, it is advisable to give an account of plural situations. However, instead of a dichotomic analysis of the legal fact opposing the monism of State law to the pluralism of unofficial bodies, it would surely be necessary to propose a double shift of the point of view. First, it means carrying out the analysis of normative systems connected with official law, in the sense that they are based on written or oral rules that a group of people are supposed to know and interpret, that they are equipped with bodies (this group of people precisely) charged with enforcing them and that people refer to them as an alternative legal system to official law. Second, it means considering the ways by which the actors perceive, understand and act in their legal environment, permanently opposing the plurality of the social norms of reference to the "unique" character of the prevailing law. Durkheim (1950, p. 144) made the protection of "personal property" the second rule of human morals. Contractual law is related to the issue of property since it concerns its acquisition and transfer, e.g. through inheritance.

The program intended to conduct research to identify -in the context of societies wholly or partly Muslim -those systems which objectify property relations between a person and an asset (contract, inheritance, gift), create a legal norm in this respect, and offer support to those who are charged with ensuring its observance. The study of legal practices concerning these relationships was done starting from a locus: that of the institutions in charge of property management.

Our intention was thus to explore property phenomena and to offer an ethnographic description of the practices linked to them. It included the identification of the appropriation modes of an asset, of the means allowing one to attest to rights of ownership, of the channels available in order to assert these rights, of the ways of reasoning in those instances, of the part played by the oral or written language, and of the conceptions of property as they operate "in action". What is often characteristic of the anthropology of the contract is its propensity to model the transactions and to put them in a deterministic sequence. In that sense, the contract is not studied in and for itself, as an instrument of transaction formalization, documentary support, evidence, reference, etc. Our aim was thus to look for what was left aside and to carefully describe it.

All in all, the management of property rights is the focal point of norms and methods of using and referencing them. For instance, the analysis of a conflict about a question of property and its resolution can make the laws on property in force in a certain context explicit, the various ways in which the people concerned refer to it, the form that a disagreement can have as soon as it is taken up by an authority entrusted to deal with it, but also the relations between law or other types of normativities and the structure, even the nature, of these relations such as they are perceived from the legal places.

*

The Anthropology of Islam and of Muslim countries is deeply influenced by culturalism, where Islam becomes the central and dominant code of significances. This is also true for anthropological investigations on Muslim minorities in Europe. Islamic law is thus, with Clifford Geertz, perceived as a cultural code of significance making it possible to interpret the world: "The 'law' side of things is not a bounded set of norms, rules, principles, values, or whatever from which jural responses to destilled events can be drawn, but part of a distinctive manner of imagining the real." (Geertz 1983, p. 173). In this hermeneutic project, "the words are keys to understanding the social institutions and cultural formulations that surrounds them and give them meaning" (Merry 1988, p. 886).

Our aim was also to break away from the postulate of cultural exceptionality of legal interpretations in totally or partially "Muslim" societies. The works on law in these societies seem to focus on looking for the Islamic portion of law and to stop there -the multiplication of the works on properties, waqf, habus, on Islamic finance and more largely on "Islamic law" is a perfect example. Still analyses to determine to what extent such or such a portion of law is Islamic, and to what extent such or such a portion of law should be explained or not by any historical development of Islamic law, tend to impose their structure to the legal phenomena and activities, instead of seeking to discover how they operate. In doing so, research fails to describe the phenomena it should nevertheless document and, in particular, the ways people understand and express their understanding of any given situation, to take its bearing with respect to a context and its constraints, and to behave and act in a more or less orderly fashion inside a similar context delineated spatially and temporarily. Still, even in situations where an Islamic genealogy of things can be identified (such as family law in numerous countries), an a priori characterisation of "Islamic law" fails to depict what people do in a particular legal context when they address issues related to family, acts which can only be carried out by describing people's practices outside any pre-established interpretative framework. What can we then say of these domains where the relation to Islam cannot even be established genealogically?

It should be clear by now that the purpose of this program was not to force the secret of an "exotic" legal universe. On the contrary, it attempted to describe this activity without any prejudice on what, from a legal viewpoint, a priori differentiated these societies from other contexts. It does not even postulate the existence of such differences. In other words, this program is related to legal practices in an overwhelmingly Muslim environment, not to the Islamic culture observed through the prism of law. To tell the truth, the Islamic culture is but one of the multiple components of the context, which is always unique and never uniform, in which the law practices are deployed. To assume that this cultural component is primordial runs the risk of not paying sufficient attention to the other possible components, as is such with many things which the members of the judiciary and legal environment of these societies conveniently focus on during their actions. This also involves the risk of overestimating the impact of culture. The corollary of culturalism is non-translatability. Thus, such a concept formulated in Arabic could not be perceived in French adequately because its essence would only be accessible in the language it was originally formulated. We consider, on the contrary, that any phenomenon, regardless of the language in which it is expressed, remains translatable into another language and accessible to observation and to description. This implies, however, "rather than supposedly reading over the shoulder of an imaginary native a text completed in a culturally standardised form [to read] line after line the continuous production of a real autochthonous speech." (Moerman 1987, p. 5). * This volume on Sudan is an excellent example of what can be achieved in the anthropological study of law, in general, and of property, particularly in a Muslim environment. Its chapters, which are all empirically documented, detail the ways in which some conflicts, e.g. on land issues, are dealt with, how the law is produced, managed, used and also dodged, how conflicting norms are practically attuned. It will certainly break grounds for further studies in the praxeological spirit of the program in which it was part advocated.

Bibliography

  Dupret, B, Berger, M, Al-Zwaini, L (eds) 1999, Legal Pluralism in the Arab World, Kluwer Law International, The Hague. Durkheim, E 1950, Leçon de sociologie, PUF, Paris. Geertz, C 1983, Local Knowledge: Further Essays in Interpretive Anthropology, Basic Books, New York.

As an introductory reading on legal pluralism, seeDupret et al. 1999.


Baudouin Dupret

Yazid Ben Hounet

come

Anthropological Perspectives on Law and Property in Algeria Introduction

Yazid Ben Hounet & Baudouin Dupret

With a surface area of 2.5 million km², Algeria is the largest country in Africa -the tenth largest in the world -and one of the continent's leading economic powers. Its economy is still highly dependent on oil and gas exports. It has the highest GDP per inhabitant in North Africa (US$ 7,534 in comparative purchasing power figures from 1 January 2014). and the fourth highest GDP on the African continent (US$ 206.1 billion in 2013). With close to 40 million inhabitants (38.7 million on 1 January 2014), of which 98% are Muslims, Algeria takes ninth place in the countries of the Muslim world. However, in spite of this privileged place on the African continent, in the Muslim world and in the MENA region (Middle East and North Africa), Algeria remains poorly known, and the works relating to contemporary Algerian society published outside of Algeria are rare. The colonisation of Algeria by the French, and the Algerian War of Independence, are the object of many publications in the French-speaking and English-speaking world alike 1 ; but publications in the social sciences on Algeria today are still limited in number, compared with those on Morocco and Egypt for example. This observation is valid in particular for social and cultural anthropology, a discipline which up to the early 1990s was somewhat despised by the authorities. They considered it to be a colonial science 2 , and suspected it of promoting the theses of, and giving a university base to, Berber movements [START_REF] Moussaoui | La pratique de l'anthropologie en Algérie[END_REF]. It was only in the 1990s, as the country began to embrace a multiparty system, that departments specialised in anthropology started to develop in Algeria 3 . However, the violence and insecurity of the "black decade" (décennie noire) 5 of violence (from the early 1990s to the early 2000s) made thorough field research almost impossible. Consequently, ethnographically documented anthropological works based on data collected directly in the field have been limited in number 6 . This book, which focuses on law and property in Algeria from an anthropological perspective thus seeks to contribute, however modestly, to our understanding of Algerian society today, through its relationships to property and to law. Beyond this, the objective of this book is to propose, in a comparative perspective proper to anthropology, new theoretical and 1 As regards the French-speaking world, let us mention the works of Charles-Robert Ageron, Mohamed Harbi, Benjamin Stora, Daho Djerbal, Gilbert Meynier, Sylvie Thénault, Malika Rahal ; as regards the Englishspeaking world, the works of James McDougall, Todd Shepard. 2 Ahmed Ben Naoum speaks of this frustration, linked with « the guilty conscience of belonging to an 'ethnographied' society » (1993: 29). 3 Anthropology (social and cultural), the daughter (offspring) of colonialism, in Claude Lévi-Strauss's words, had a singular fate in the Algerian academy. Criticised and rejected in the first decades following Independence, the discipline is today advocated by numerous scholars. Courses (masters, doctorate, etc.) in anthropology are also being developed in Algerian universities and research centres. Some works exist on criticism of anthropology as colonial knowledge (notably [START_REF] Lucas | L'Algérie des anthropologues[END_REF]; and a few on the analysis of the institutional development of anthropology in Algeria since Independence (notably [START_REF] Moussaoui | La pratique de l'anthropologie en Algérie[END_REF]and publications by the CRASC on the social sciences in Algeria). These academic publications address a number of debates on the modes and types of knowledge produced on Algeria, as do the scholars in anthropology and the related university courses. methodological perspectives by which to apprehend the anthropology of law in a Muslim context. Algeria, as a post-colonial and post-Socialist State, whose population is overwhelmingly Muslim, proves to be a particularly interesting case to study. To focus on property law in practice, on the conflicts inherent to it, and on the strategies deployed to circumvent the law, is a particularly fruitful perspective from which to view the effects of a rapidly changing society. In this Introduction, we shall first explain the theoretical framework of our book -property law from an anthropological perspective -and our aim -to substitute the anthropology of Muslim law for a legal anthropology in a Muslim context. Secondly, we shall discuss certain specificities of property law in the post-colonial and post-Socialist State which is Algeria. We shall, lastly, present the various chapters of this book.

Law, anthropology and property

In their introduction to the book Changing Properties of Property, Franz von Benda-Beckmann, Keebet von Benda-Beckmann and Melanie G. Wiber (2006: 2) emphasise that: "Property is always multifunctional (…). It is a major factor in constituting the identity of individuals and groups. Through inheritance, it also structures the continuity of such groups. It can have important religious connotations. And it is a vital element in the political organisation of society, the legitimate command over wealth being an important source of political power over people and their labour, no matter whether we think of domestic or kinship modes of production, capitalism or communism. Property regimes, in short, cannot easily be captured in a one-dimensional political, economic or legal model". In addition to the multifunctional aspect of property, these authors remind us that the property models in force, which claim universality, are in fact largely based on Western legal categories. The most important of these is the notion of private and individual possession, "often regarded as the apex of legal and economic evolution as well as a precondition for efficient market economies" (von Benda-Beckmann, von Benda-Beckmann and Wiber, 2006 : 3). The issue of property and its transmission is at the very heart of any socio-anthropological investigation. It founds the economic and political relations of a society, and these relations constitute the central object of legal regulation. Social changes are also reflected in the evolution of property relations, as has been emphasised in anthropology, as well as in other disciplines of the human and social sciences. Durkheim (1950: 152), for example, considers the protection of a "human person's property" as the second rule of human morality. He regards contract law as an extension of this situation, in the form of the acquisition and transfer of property, of which inheritance is one particular mode. Contrary to classic conceptions, for which property is linked to work and is a kind of natural law -John Stuart Mill asserts that property does not imply anything other than the right to one's personal talents, hence to what can be produced by applying these -, Durkheim remarks that property, and consequently its transfer as well as the kinship links justifying it, is a social fact. But a social fact may eventually assert itself as the "nature of things" by its sole existence, when "a certain arrangement of facts and circumstances appears unavoidable once its existence has been acknowledged" [START_REF] Foriers | [END_REF]. Kant considers property as an intellectual link since it associates a person and a thing independently from any necessity of a physical link. This relation implies reciprocity, since for other people to admit that you have a right on something they do not possess, the ego itself must admit the equivalent right of other people on certain goods. And for this reciprocity to be established, the things must be possessed originally by a collectivity. Durkheim, starting from the Kantian conception, seeks a definition of the right to property which is abstracted from the particular modalities that it may have taken in different times and places. The first element he identifies is the existence of an appropriable thing, whose definition obviously varies from one population to another, just as does the definition of who is entitled to possess. The second element is the relation between the owning subject and the owned thing, which Durkheim specifies as the exclusive enjoyment of the good, even if the effective enjoyment is postponed, as in the case with usufruct. This prevents other people from taking advantage of it. The question of this relation is also at the heart of the definition of property suggested by Levi-Strauss. It is no longer an objective relation between the subject and the object, but a relation between people, a relation with other people and the social structure (2002: 100), which can be described as "mediatised" by the good owned. We should also mention the materialist approach, represented by Godelier, for example, who considers that forms of property express relations of production. Law is considered here as a superstructure concealing the actual content of these relations of production, sometimes even out of step with them (law as only a fiction). The study of property obviously cannot be reduced to Kant, Durkheim, Lévi-Strauss and Godelier. The aim here is to emphasise that all these authors engaged in a quest for an ontology of property, that is, a search for the essential properties which provide the "essence" of property. In certain respects, however, this ontology is reduced to a metaphysical approach, inasmuch as the essential nature of this « essence » worries these thinkers more than the conditions of its deployment. We shall suggest, from the Algerian context, that one should hold on to this issue of the essence of proprietary right in order to explore its praxeology, in other words, to describe ethnographically the related practices. This involves identifying the modes of appropriation of a good, the ways of certifying a right to property and exercising this right, the reasoning employed to establish causes, effects or relations, the role played by the spoken or written word, and the way important notions such as the person-good, movableimmovable, property-ownership, property-possession distinctions, etc., play out in the real.

From an anthropology of Muslim law to an anthropology of the law in a Muslim context

This book seeks, moreover, to break with the postulate of cultural exceptionality evident in legal interpretations concerning totally or partially « Muslim » societies. The works on law in these societies seem to focus on looking for the Islamic portion of the law, and to stop therethe multiplication of works on property, waqf, habus, on Islamic finance, and more generally on « Islamic law » is a perfect example. Determining to what extent such and such a portion of law, orthodoxically or heterodoxically, is Islamic, and to what extent such and such a portion of law should be explained or not by the historical development of Islamic law, tends to impose its structure on the legal phenomena and activities, instead of seeking to discover how they operate. In so doing, research fails to describe the phenomena it should be documenting and, in particular, the ways people understand, and express their understanding of, any given situation, take their bearings with respect to a context and its constraints, and behave and act in more or less orderly fashion within a similar context delineated spatially and temporarily. Even in situations where an Islamic genealogy can be identified (such as in many countries' family law), a priori characterisation of « Islamic law » fails to depict what people actually do in a particular legal context, when they address issues related to family. These are things which can only be investigated by describing people's practices without imposing any pre-established interpretative framework. What, then, of the domains where the relation to Islam cannot even be established genealogically! Although this book builds on material derived from legal practices observed on the Algerian territoy, it should be clear by now that its purpose is not to lay bear the secrets of some « exotic » legal universe. On the contrary, it attempts to describe these practices without prejudging what, from a legal viewpoint, may differentiate these societies from other contexts.

It does not even postulate the existence of such differences. In other words, this book relates to legal practices in an overwhelmingly Muslim environment, not to Islamic culture observed through the prism of the law. Islamic culture is but one of the many components of the context, which is always unique, never uniform, in which legal practices are deployed. To assume that this particular cultural component is fundamental incurs the risk of not paying sufficient attention to other possible components, the things on which the members of the judiciary and legal environment of these societies focus. It also risks overestimating the impact of culture. The corollary of culturalism is non-translatability; a concept formulated in Arabic could not be adequately perceived in French because its essence would only be accessible in its original formulation. We consider, on the contrary, that every phenomenon, regardless of the language of its expression, remains translatable into another language and accessible to observation and to description. This implies, however, « rather than supposedly reading over the shoulder of an imaginary native a text completed in a culturally standardised form [to read] line after line the continuous production of a real autochthonous speech. » (Moerman, 1987: 5). It remains for us to justify the use of legal data derived from totally or partially Muslim contexts, while refusing to substantiate cultural differences. First, there are no grounds to consider a given context as more relevant, appropriate or worthy of interest in itself than any other. As this context has been largely overdetermined until now by a reference to Islam, it is not uninteresting either to show when this reference is empirically documented and when it appears as postulated and not demonstrated. If this book succeeds in demonstrating that similarities or difference between contexts lie in many factors other than that of religion, it will have proved worthwhile, in a general atmosphere where human beings' « common humanity » seems to be denied in the name of conflicts between cultures and ineffably distinct civilisations (and, conversely, where humanity often stops at the frontiers of a « common religion »). At the end of the day, certain specificities might well be attributed to the existence of an Islamic referent, but they cannot be considered to be untranslatable. On the contrary, « their significations can be known and are naturally known: they are governed by grammatical conventions which can be determined and are part of the conceptual equipment of the human species, in spite of the differentiated empirical distribution of their effective usage and of the different types of language games observed in different cultures » (Coulter, 1989: 101).

Law and property in post-colonial and post-Socialist States

In these States, policies on property law can be explained partially by the country's particular historico-political conditions. However, these cannot account for the bulk of local practices (far from it, as we shall see later). In this Introduction we shall nevertheless depict the major features of Algerian policies in this domain, but only briefly, because the first chapter of this book inventorises and analyses the laws passed since Independence. A recent volume on colonial law (Bras, 2015) can serve as our starting point. Through a close examination of the themes of property, legal literature, judicial personnel and attorneys, this work provides the building-blocks for an anthropology of law in Algeria. We can see how profoundly law is a historically situated phenomenon. In the case of colonial law, it is encapsulated in a specific time frame, with a precolonial "before", made of major discontinuities, and the "after" of independence, with important effects of continuity. We can see how greatly colonial law disrupted the local, indigenous understanding of normativity: under the pretence of systematising the pre-existing law, colonial (Muslim) law actually constructed something new. Land law is a very good example of this, since it was based on incompatible tendencies: it founded law on universal principles, while at the same time permitting colonial annexation of land. Colonial doctrine presented Islamic norms as the law of an imperfect civilisation in need of a civilising process of systematisation. After independence, we can observe how little the political break was accompanied by a legal one, but rather by the refurbishment of the colonial legacy in national terms.

As explained by Robert Young (2001 :57): « The postcolonial is a dialectical concept that marks the broad historical facts of decolonisation and the determined achievement of sovereigntybut also the realities of nations and peoples emerging into a new imperialistic context of economic and sometimes political domination. The experience of that new sovereignty typically encouraged the development of a postcolonial culture which radically revised ethos and ideologies of the colonial state and, at the same time, reoriented the goals of the independence movement towards the very different conditions of national autonomy ». We cannot understand Algerian society today if we ignore its colonial past. Colonisation and the War of Independence profoundly affected the imaginary and the representations of Algerian society, as well as the policies implemented by the newly independent Algerian State, but also by the POLISARIO Front (the Western Saharan liberation movement) and the Sahrawi Arab Democratic Republic (SADR) (see Alice Wilson's contribution in this volume). Several studies in this book account for the transformations of the ideologies and representations surrounding the issue of property and its legitimacy in post-colonial Algeria, as well as in the specific case of the Sahrawi refugee camps, under the authority of the SADR, in the region of Tinduf. Since property is closely linked to the processes of constitution of individual and collective identity, it has a singular place in the development of States and their societies. The issues surrounding home-ownership reflect the transformations of such ideologies and of the economies proper to every State and every society. For example, the Socialist policies, in particular concerning agricultural land, the establishment of collective agricultural concerns, agrarian reform, etc., implemented by the newly independent State in the 60s and 70s, were meant to be a radical departure from those imposed by the colonial State, and thereby to restore the sovereignty of the Algerian people on its land 7 . Do we need to go over this again? During the colonial period, Algerian society was profoundly affected by two major policies introduced by the French authorities: the Code of Indigenous Status and an unprecedented Dispossession of indigenous land rights. The indigenous regime, a regime of exception applied to the natives, was implemented by the Arab offices in the first days of the conquest (1830), then formalised as from the 1870s and confirmed by the act of June 28 1881. The Code of Indigenous Status legally enshrined the separation between the Muslim populations and the French citizens. The Crémieux decree, promulgated in 1870, granted French citizenship to the Jews of Algeria. The Muslims of Algeria were submitted to the justice of the qadi (Muslim judges) in matters of personal status, but also to the French laws and to specific, individual and collective measures (fines, cantonnement, receivership) [START_REF] Ageron | Histoire de l'Algérie contemporaine, De l'insurrection de 1871 au déclenchement de la guerre d'Algérie[END_REF]. In the Southern territories, the native populations were administered by the militaryunlike the department of the North [START_REF] Valet | Le Sahara Algérien. Étude de l'organisation administrative[END_REF][START_REF] Hounet | Des tribus en Algérie ?[END_REF]. To this exceptional legislation was added large-scale dispossession of indigenous land rights. Jean Claude Vatin [1983: 125] notes, echoing the overview made by Charles Robert Ageron, that « between 1871 and 1919 close to one million hectares (897,000) were handed over to the 7 « 'Postcolonialism' commemorates not the colonial but the triumph over it. The 'post' marks the many remarkable victories that should not be allowed to fade into the amnesia of history. The postcolonial era in its name pays tribute to the great historical achievements of resistance against colonial power, while, paradoxically, it also describes the conditions of existence that have followed in which many basic power structures have yet to change in any substantive way » (Young, 2001, 60).

settlers. [...] The Muslims had lost, in 1919, 7 and a half million hectares, which the State and individuals, the major capitalist societies, shared out. » More than 2,700,000 hectares, in 1940, representing 35-40% of the arable land in Algeria, were then appropriated by the settlers and the major European companies (Lapidus 2002: 589). Both these historical realities, together with the post-colonial and post-Socialist developments experienced by Algeria, help to explain, at least partially, the importance of two issues addressed in the chapters of this book: 1) a certain mistrust of the rule of law and the authorities supposed to enforce it, along with practices for circumventing it; 2) the importance of conflicts related to land rights, whereas the latter only represents today a small proportion of the general economy of property law, as Ammar Belhimer reminds us in the first chapter. After a period of Socialism and Collectivism, Algeria engaged in privatisation policies and, especially from the 1990s, introduced a market economy. The role played by the Algerian State in the regulation of this market economy is still substantial and a closer look shows us that switching from a Socialist-style planned economy to a market economy has been, and still is, an ambiguous move, and a challenge, which affect property law. In this no man's land between Socialism and the market economy, the use of law is problematic. Circumventing Strategies to circumvent and abuse the law have developed. Corruption is on the increase (Hachemaoui, 2013). Have we switched, then, in Algeria -to repeat the question David Stark and Laszlo Bruszt asked concerning Central Europe (1998) -« from plan to market or from plan to clan ? ».

Presentation of the Chapters

The relations between law and property should not be explained solely through the weight of culture, of the socio-political system and/or of history. The fact that Algeria, but also the Sahrawi Arab Democratic Republic (SADR), are post-colonial and post-Socialist States, does not in itself account for all the practices observable in situ. The general context and the singular socio-historical conditions are part of the specificity of the Algerian State and its society, but have not asserted themselves everywhere, nor in the same way. Our aim was hence to shed light on the general context and the global issues at play in Algeria, in terms of property law, without presenting them necessarily as justification of the practices reported in the different chapters of this book. We hoped simply to provide the uninformed reader with an overview of some general issues pertaining to property law in this country. The ethnographic approach we espouse involves specific case studies aimed at emphasising practices, interpretations and justifications in their own contexts, without presupposing the weight of history, of culture, or of the socio-political system. This approach is in line with our criticisms of certain major works relating to legal anthropology and property, as well as of the anthropology of Muslim law, as explained above. The research presented here covers many aspects of the subject of Property and Law, using different types of fieldwork from many Algerian regions, including the Sahrawi refugee camps near Tinduf. It foregrounds, through the use of cases studies, the ethnographical, praxeological, and contextual dimensions of property and law. As such, this research provides a more realistic view of practices of law and property in Algeria today. It deals with the issue of legitimate claims in property, which can be invoked in different ways. Ammar Belhimer (chapter 1) explains that the legal corpus of independent Algeria has shown a recent and precarious rehabilitation of private property law. This rehabilitation is still embryonic and not straightforward and goes against the long praised pre-eminence of public ownership, as the foundation of justice and social equality. The first constitution of the Algerian State, promulgated on 10 September 1963, did not address the issue of property, whether private or public. Subsequently, the National Charter, then the Constitution of 22 November 1976, mentioned State property, to which were ascribed quasi-mythical qualities such as absolute title and inalienability, which were deemed to constitute the highest form of social property. Recent developments betray a two-fold evolution: the maintenance of State property on the agricultural lands abandoned by the settlers in the aftermath of Independence; and the privatisation of all the other immovable goods or economic activities. Land dispossession processes during French colonisation and legal land policies after Independence led, at least in Northern Algeria, to the existence of two distinct agricultural sectors with different modes of appropriation of land resources. The first sector includes the most fertile lands of Algeria, the plains, which were seized by the French colonisers, and were nationalised after independence. The other sector comprises the peripheral lands of the piedmont and mountain areas on which most of the Algerian peasantry were relegated. Whereas the historic forms of land appropriation were perpetuated on these peripheral lands, they were prohibited on most of the lands in the plains, first by the French colonisers and then by the Algerian State due to its collectivisation policy after Independence. On the basis of a survey of land dynamics conducted in Algeria's Lower Cheliff plain, Hichem Amichi, Marcel Kuper, Sami Bouarfa (chapter 2) show that the old modes of appropriation of resources have returned in force regarding public land, after the process of decollectivisation started in 1987. These old forms, previously restricted to the piedmont areas, have become, despite prohibition by the State, the main regulators for access to productive resources on the most fertile lands in Algeria. These authors analyse the specificities of land appropriation in a post-Socialist context through two main social categories of Algerian farmers: 1) the beneficiaries of rights to public land use, former workers on State farms and colonial domains, on the one hand, and 2) tenants or sharecroppers, on the other hand, often Algerian peasants dispossessed of their land by French colonisation. They discuss the opposition between the right to use the land and the legitimacy gained by working the land. Their analyses are based on their observations on the proliferation of informal arrangements between the two categories of stakeholders who work the public lands at present. The contribution of Tarik Dahou (chapter 3) illustrates the ambiguities of how the law is appealed to, but also circumvented, in the framework of the exploitation of maritime resources (corals) in Eastern Algeria. The impact of market economy penetration and of the Algerian State's alignment with international standards for natural resources management is also addressed. One of the issues is the legal mechanisms used regarding concessions of maritime resources in Eastern Algeria. Use of natural resources in the Mediterranean is governed by multiple norms, operating at global and local levels. Yet the academic literature on nature conservation does not sufficiently explore the national and local impacts of conservation processes. Since Algeria's ratification of international conventions on biodiversity (CBD, RAMSAR, CITES), the country has been engaged in re-formulating its national conservation policies. It has also been putting considerable effort into fulfilling its international commitments. Changes in legislation regarding coastal areas and new projects extending the maritime border of coastal national parks, illustrate this. The National Park of El Kala (PNEK), one of the most emblematic Mediterranean terrestrial and marine biodiversity sites, is a good illustration of how Algerian protagonists appropriate nature conservation policies at local and national levels. The example of PNEK shows how international nature conservation objectives can become blurred at the local level, as attempts to apply international conservation norms produce inequalities and pose threats to biodiversity. Although State legislation permits concessions regarding natural resources within the PNEK, in practice, the exploitation of marine resources is shaped by interactions between public and private networks. The contradictions between State-regulated access rights and exclusions are further exacerbated by the ambiguous relations between the State bureaucracy and local protagonists. In contrast to world nature conservation recommendations, the nexus of local powers operating in the PNEK has led to intensified commodification of nature, as well as social conflicts over the appropriation of natural resources. Tarik Dahou's analysis focuses on the normative mechanisms and the disciplinary techniques used by the Algerian State to govern nature. The comparative study of two marine concessions reveals two dimensions of biopolitics: whereas, in the first concession, governed by national legislation, the enforcement of the law is obstructed by the multiplicity of norms and incomplete monitoring, in the second, an 'illicit concession', conservation norms are enforced through disciplinary methods that go beyond the law. Judith Scheele (Chapter 4) addresses struggles over land and legitimacy in the Soummam Valley. In Algeria, property rights, as experienced on a daily basis, are notoriously slippery. Rights to real estate in particular, even where they are legally defined, always also draw on notions of history, merit and political influence, and are hence not easily contained in the law. With the frequent and often violent changes in legal regime, moreover, clear definitions of property are only rarely achieved, even in contemporary transactions. This is particularly visible in cities, but it remains equally true in the country, especially where valuable agricultural land is concerned. Land rights remain deeply political and contextual, as they do not only define rights of access and ownership, but also make statements about social and political legitimacy and 'sound' definitions of history: in other words, conflicts over property rights are both intensely local and fought out with reference to larger moral frameworks, more often than not that of the Algerian nation. This is perhaps why concrete case studies of these tensions are few and far between. Judith Scheele's paper proposes one such case study. It describes longstanding conflicts over property rights in one small part of the Soummam Valley in Kabylia, which, while they have their roots in pre-colonial times, have recently led to renewed social protest. After tracing the intricate history of these conflicts, the chapter analyses the terms in which they are fought out locally, before relating them to broader debates within the country as a whole. Beyond this idea of legitimacy, there emerges the question of how people refer to the law and the local norms. Yazid Ben Hounet's paper (chapter 5) focuses on land-tenure in steppe-land environments (Naâma Province). He argues that the issue of land-tenure in Algeria has been and remains a problematic and a major challenge because of the policies of dispossession, nationalisation and socialisation conducted during the colonial period , and after the country's independence (1962). The paper deals with the application of property law concerning land-tenure in Algeria, focusing on the enforcement of the law giving access to agricultural land (1983) in a steppe-like province in Western Algeria (Naâma). It presents and analyses conflicts that have emerged from the enforcement of this law. It discusses the issue of agricultural land-tenure and raises the question of law by analysing the way people refer to the law in land-tenure disputes. These analyses enable us to understand the operative norms and rules governing agricultural land-tenure; the ways different protagonists refer to the lawthat is, the uses of the law and the role of law enforcement institutions (judicial and / or administrative institutions) -, as well as the interpretations of the law by these protagonists. To gain insight into how individuals are affected by and also utilise multiple legal and normative systems on the everyday level, Nejm Benessaiah focuses, in chapter 6, on inheritance disputes regarding land tenure in the Beni Isguen oasis (M'zab). Historically, the Mozabites of Ghardaia, Algeria, were governed by the c azzaba (priesthood), who effectively ruled as a theocracy, punishing unsanctioned behaviour through tebria (excommunication). Local disputes were resolved according to 'urf, often translated as customary law, consisting of encoded verbal rules or agreements. Resources such as land tended to be managed in common, presided over by the family patriarch. A key to successful colonial rule was allowing Muslim communities to continue practicing the Islamic faith undisturbed, including the Sharia. Later, State law became a further complicating factor in power relations between regulatory systems. The multiplicity of legal regimes has even afforded a kind of 'forum shopping' by litigants, based on opportunistic self-interest, as the author found in the M'zab. While formal modes of local governance were denigrated by the State, informal normative order has also been slowly eroded by conflict with the new ideas arrriving through the global mass media. This chapter investigates how the presence of multiple systems of law influences the decision-making process of disputants in Beni Isguen, Ghardaia. In the very specific context of Sahrawi refugee camps, Alice Wilson addresses the issue of compensation when property has been lost (chapter 7). Refugees may, if they do not return home, be eligible for compensation for property lost upon going into exile. Her paper considers the question of refugees being eligible for, and receiving, material compensation from other refugees in internal disputes taking place in exile. Sahrawi refugees from Western Sahara have been in exile in Algeria since 1976, following the still-unsettled conflict over these territories previously colonized by Spain. Sahrawi exiles live in refugee camps in Algeria run as a "state within a state" by an administrative fusion between the POLISARIO Front and the partially recognised authority it founded, the Sahrawi Arab Democratic Republic (SADR). Drawing on ethnographic fieldwork conducted in the refugee camps from 2006 to 2012, this chapter examines how pre-exile practices of compensation payments in internal disputes virtually disappeared in the early period of exile. This shift reflected practical and ideological reasons: in practical terms, refugees were dispossessed and thus divested of property with which to make payments, and ideologically POLISARIO focused on popular justice, which encouraged questions of compensation to be deferred until after national liberation, and discouraged questions of tribes, the social context in which compensation payments had previously occurred. Nevertheless, after the ceasefire in 1991, the judicial administration in the refugee camps was professionalized and this, together with a rise in living standards in the camps, had the paradoxical consequence that compensation payments in internal disputes reappeared to a limited degree, and in the context of tribes. In this volume, the reference to Islamic law only becomes clear in the last chapter, which focuses on family law and inheritance; more specifically, the chapter concerns the practices of transmission of property in situations of kafala (legal fostering). Emilie Barraud explains that, since 1984, Algerian legislation has provided that « adoption (tabanni) is prohibited by the shari'a and the law » (art. 46). By using a doubly imperative tone and referring to the authority of Islamic law, the Algerian lawmakers intend to underscore the firmness of this official position, and to place it beyond discussion. The external observer will confirm that « adoption does not exist in Algeria since Islam forbids it ». However, ethnologies of elective parenting lead one to nuance this assertion. Adoption as defined in French law has no equivalent in Algerian law, but this does not prevent certain forms of institutionalised social parenthood (such as legal fostering, kafala), as well as illegal adoptions. The Family Code forbids adoption, but has substituted it since with another mode of family integration, the legal fostering, or kafala, of a minor, which is the commitment to maintenance and protection of a minor, but without the latter being endowed with the status of a legitimate child. Thus, under the authority of Islam, the norm would be the absence of adoption. If we admit that the kafala is a form of adoption, the norm would be that the « adopted » child is concerned neither by the transmission of the name, which is one of the effects of legitimate filiation, nor by the rules of inheritance attached to that legitimacy. Yet in many cases, « conservatory » provisions are taken by the parents of adopted children, in the form of legacies, donations or sales, to « protect » the fostered child. All of these are are focused on circumventing the Islamic prohibition on adoption, and present new strategies of action. Throughout the book, legal practices can be explained more by other criteria than by Islamic norms (in particular switching from a Socialist system to a market economy; the administrative constraints and difficulties encountered by a State in the making, dominated by the annuity economy; and the experience of exile, as regards the Sahrawi refugee camps). Even in the last chapter, the practices of transmission of goods to fostered children (makful), although strongly influenced by Islamic law, cannot be explained solely by it, far from it. Family law is often examined in legal studies of Muslim societies, because it was long considered to be the last bastion of a declining Islamic law. Although the rule of unequally shared inheritance according to the sex of the heir has been written about extensively, the specific domain of succession has remained largely unexplored. Additionally, the a-historical assertion of a casuistic theory has attracted more research than has the ethnographic study of the practices surrounding transmission of goods. The texts assembled in this volume offer an overview of legal practices regarding property on the Algerian territory today. They can enable us to establish comparisons with other contexts in the Muslim world. What are the prevailing practices? What place do Islamic norms concretely occupy nowadays regarding property law? On what registers and foundations do these practices rest? Rather than giving ready-made answers to these questions, we propose to go back each time to the ethnography of legal practices, to remind us that these practices can become totally meaningful only in their own contexts.

Cf. on this issue Luis[START_REF] Martinez | La guerre civile en Algérie[END_REF] and Abderrahmane[START_REF] Moussaoui | De la violence en Algérie. Les lois du chaos[END_REF]. AbderrahmaneMoussaoui (2006:13) refutes the term « Civil war » used by Luis Martinez as it "is not quite appropriate when this violence remains 'localised' in certain regions and limited to certain categories". We shall use the word used locally to define this decade of violence.

Among the rare anthropologists to carry out field research during the 1990s and the early 2000s, we can mention Abderrahmane Moussaoui, Susan Slyomovics, Judith Scheele and Tassadit Yacine.