Paul Pilet

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (118)384.12 Total impact

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    ABSTRACT: Hydrogels are a suitable scaffold material for a variety of tissue engineering applications. However, these materials have a weak structure and require reinforcement. Integrating electrospun fibers could strengthen material properties. This study created fibers and evaluated the influence of the presence of polar head groups within a polysaccharide backbone following functionalization: silated-hydroxypropyl methylcellulose (Si-HPMC). Electrospinning is a multi-parameter, step by step process that requires optimization of solution and process parameters to understand and control the process. Fibers were created for 2%–3% wt/v solutions in water and ethanol. Viscosities of solutions were correlated with spinnability. Variations on process parameters did not reveal major variation on fiber morphology. Once controlled, the process was used for HPMC/Si-HPMC mixture solutions. Solubilization and dilution of Si-HPMC were made with common solvents for electrospinning. Two forms of polymer conformation were electrospun: silanol ending and silanolate ending. Microstructures and resulting nanofibers were analyzed by scanning electron microscopy (SEM) and Energy Dispersive Analysis (EDX). The results show the feasibility of our strategy for creating nanofibers and the influence of polar head groups on electrospinnability.
    12/2015; 1(1):44-57. DOI:10.3390/gels1010044
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    ABSTRACT: The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE) could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX) C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (-31.9%; p < 0.001 vs. OVX mice) and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP) activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.
    Nutrients 11/2015; 7(11):9265-9284. DOI:10.3390/nu7115465 · 3.27 Impact Factor
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    ABSTRACT: Objectives To develop an animal model of mandibular osteoradionecrosis (ORN) using a high-energy radiation source (as used in human therapeutics) and to assess the role of tooth extraction on ORN development. Materials and methods (study design) Ten animals were irradiated with a single 35- or 50-Gy dose. Three weeks later, the second left mandibular molar was extracted from three animals in each group. Nine weeks after irradiation, the animals were euthanized, with an injection of contrast agent in the bloodstream to highlight vascularization. Mandibles were harvested and studied using micro-CT, histology, tartrate-resistant acid phosphatase activity and scanning electron microscopy. Results This study demonstrates that a single 50-Gy dose associated with molar extraction is necessary for ORN development. In these conditions, absence of healing of the mucosa and bone, dental effects, fibrosis, an increase in osteoclast activity and a decrease in vascularization were observed. We also determined that molar extraction increases the impact of the cellular effects of radiation. Conclusion The mandibular ORN animal model was validated after 50-Gy irradiation and molar extraction. The results of this study therefore support an animal ORN model and tissue engineering strategies will now be developed to regenerate bone for patients with head and neck cancer.
    Journal of Cranio-Maxillofacial Surgery 11/2015; 43(9):1829-1836. DOI:10.1016/j.jcms.2015.08.016 · 2.93 Impact Factor

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    ABSTRACT: This study used a fractal bifurcation bench model to compare 6 optimization sequences for coronary bifurcation provisional stenting, including 1 novel sequence without kissing balloon inflation (KBI), comprising initial proximal optimizing technique (POT) + side-branch inflation (SBI) + final POT, called "re-POT." In provisional bifurcation stenting, KBI fails to improve the rate of major adverse cardiac events. Proximal geometric deformation increases the rate of in-stent restenosis and target lesion revascularization. A bifurcation bench model was used to compare KBI alone, KBI after POT, KBI with asymmetric inflation pressure after POT, and 2 sequences without KBI: initial POT plus SBI, and initial POT plus SBI with final POT (called "re-POT"). For each protocol, 5 stents were tested using 2 different drug-eluting stent designs: that is, a total of 60 tests. Compared with the classic KBI-only sequence and those associating POT with modified KBI, the re-POT sequence gave significantly (p < 0.05) better geometric results: it reduced SB ostium stent-strut obstruction from 23.2 ± 6.0% to 5.6 ± 8.3%, provided perfect proximal stent apposition with almost perfect circularity (ellipticity index reduced from 1.23 ± 0.02 to 1.04 ± 0.01), reduced proximal area overstretch from 24.2 ± 7.6% to 8.0 ± 0.4%, and reduced global strut malapposition from 40 ± 6.2% to 2.6 ± 1.4%. In comparison with 5 other techniques, the re-POT sequence significantly optimized the final result of provisional coronary bifurcation stenting, maintaining circular geometry while significantly reducing SB ostium strut obstruction and global strut malapposition. These experimental findings confirm that provisional stenting may be optimized more effectively without KBI using re-POT. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    JACC. Cardiovascular Interventions 08/2015; 8(10):1308-17. DOI:10.1016/j.jcin.2015.05.016 · 7.35 Impact Factor
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    ABSTRACT: For craniofacial bone defect repair, several alternatives to bone graft (BG) exist, including the combination of biphasic calcium phosphate (BCP) biomaterials with total bone marrow (TBM) and bone marrow-derived mesenchymal stromal cells (MSCs), or the use of growth factors like recombinant human bone morphogenic protein-2 (RhBMP-2) and various scaffolds. Therefore, clinicians might be unsure as to which approach will offer their patients the most benefit. Here, we aimed to compare different clinically relevant bone tissue engineering methods in an "all-in-one" study in rat calvarial defects. TBM, and MSCs committed or not, and cultured in two- or three-dimensions were mixed with BCP and implanted in bilateral parietal bone defects in rats. RhBMP-2 and BG were used as positive controls. After seven weeks, significant de novo bone formation was observed in rhBMP-2 and BG groups, and in a lesser amount, when BCP biomaterials were mixed with TBM or committed MSCs cultured in three-dimensions. Due to the efficacy and safety of the TBM/BCP combination approach, we recommend this one-step procedure for further clinical investigation. Copyright © 2015. Published by Elsevier Ltd.
    Acta biomaterialia 08/2015; 26. DOI:10.1016/j.actbio.2015.08.013 · 6.03 Impact Factor
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    ABSTRACT: Spondyloarthritis (SpA) is a chronic inflammatory joint disorder that initiates at the enthesis, where tendons attach to bone through a fibrocartilage zone. At late stages, excessive bone apposition appears within the diseased enthesis. Because Wnt5a participates to normal bone formation and appears related to inflammatory processes, we investigated the role of this Wnt growth factor in inflammation-associated ossification in SpA. The concentration of Wnt5a assessed by enzyme-linked immunosorbent assay in synovial fluids of patients with SpA (2.58 ± 0.98 ng/mL) was higher than in osteoarthritic patients (1.33 ± 0.71 ng/mL). In murine primary cultures of tendon cells, chondrocytes, and osteoblasts and in an organotypic model of mouse ankle, we showed that tumor necrosis factor α reversibly diminished Wnt5a expression and secretion, respectively. Wnt5a decreased gene expression of differentiation markers and mineralization in cultured chondrocytes and reduced alkaline phosphatase activity in Achilles tendon enthesis (-14%) and osteocalcin protein levels released by ankle explants (-36%). On the contrary, Wnt5a stimulated ossification markers' expression in cultured osteoblasts and increased the bone volume of the tibial plateau of the cultured explants (+19%). In conclusion, our results suggest that Wnt5a is expressed locally in the joints of patients with SpA. Wnt5a appears more associated with ossification than with inflammation and tends to inhibit mineralization in chondrocytes and enthesis, whereas it seems to favor the ossification process in osteoblasts and bone. Further studies are needed to decipher the opposing effects observed locally in enthesis and systemically in bone in SpA. Copyright © 2015 Elsevier Inc. All rights reserved.
    06/2015; 166(6). DOI:10.1016/j.trsl.2015.06.010
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    ABSTRACT: Osteoradionecrosis of the jaw is a major side-effect of radiotherapy used in the treatment of squamous cell carcinomas of the upper aerodigestive tract. The standard reconstruction procedure is a free flap transfer of autogenous bone. A new approach using a tissue engineering strategy has shown that total bone marrow (TBM) associated with biphasic calcium phosphate (BCP) is the best combination for bone regeneration in an irradiated area. Recently, the stromal vascular fraction from adipose tissue (SVF) was described as an alternative to TBM for promoting new bone formation. The aim of this study was to identify the capacity of a freshly isolated SVF to induce new bone formation in an irradiated area. Four weeks after irradiation of the hind limbs of 15 rats, bone defects were created and filled with either SVF or TBM with and without BCP. Three weeks after the implantations, analysis showed that the BCP-TBM mixture improved new bone formation after radiation (p < 0.05). The BCP-SVF association induced significant neoangiogenesis but failed to enhance new bone formation. The BCP-SVF mixture was insufficient to enhance new bone formation in the irradiated area, suggesting that the role of the environment might be crucial for ossification. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
    Journal of Cranio-Maxillofacial Surgery 06/2015; 43(7). DOI:10.1016/j.jcms.2015.05.014 · 2.93 Impact Factor
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    ABSTRACT: Treatment of carcinomas of the upper aerodigestive tract often requires external radiation therapy. However, radiation affects all the components of bone, with different degrees of sensitivity, and may produce severe side effects such as mandibular osteoradionecrosis (ORN). Intraosseous vascularization is thought to be decreased after irradiation, but its impact on total bone volume is still controversial. The aim of this study was to compare intraosseous vascularization, cortical bone thickness, and total bone volume in a rat model of ORN versus nonirradiated rats, using a micro-computed tomography (micro-CT) analysis after intracardiac injection of a contrast agent. The study was performed on 8-week-old Lewis 1A rats (n = 14). Eleven rats underwent external irradiation on the hind limbs by a single 80-Gy dose. Three rats did not receive irradiation and served as controls for statistical analysis. Eight weeks after the external irradiation, all the animals received a barium sulfate intracardiac injection under general anesthesia. All samples were analyzed with the micro-computed tomography system at a resolution of 5.5 μm. The images were later processed to create 3D reconstructions and study vascularization, bone volume, and cortical thickness. Data from irradiated and nonirradiated rats were compared using the Kruskal-Wallis test. No animal died after irradiation. Nineteen irradiated tibias and six nonirradiated tibias were included for micro-CT analysis. The vessel percentage was significantly lower in irradiated bones (p = 0.0001). The distance between the vessels, a marker of vascular destruction, was higher after irradiation (p = 0.001). The vessels were also more altered distally after irradiation (p = 0.028). Cortical thickness was severely decreased after irradiation, sometimes even reduced to zero. Both trabecular and cortical structures were destroyed after irradiation, with wide bone gaps. Finally, both total bone volume (p = 0.0001) and cortical thickness (p = 0.0001) were significantly decreased in irradiated tibias compared to nonirradiated tibias. These results led to multiple spontaneous fractures in the irradiated group, and the destruction of intraosseous vessels observed macroscopically with the radiographic preview. This study revealed the impact of radiation on intraosseous vasculature and cortical bone with a micro-CT analysis in a rat ORN model. Hypovascularization and osteopenia are consistent with the literature, contributing a morphological scale with high resolution. Visualization of the vasculature by micro-CT is an innovative technique to see the changes after radiation, and should help adjust bone tissue engineering in irradiated bone.
    Calcified Tissue International 05/2015; 97(1). DOI:10.1007/s00223-015-0010-9 · 3.27 Impact Factor
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    ABSTRACT: Bone repair is an important concept in tissue engineering, and the ability to repair bone in hypotrophic conditions such as that of irradiated bone, represents a challenge for this field. Previous studies have shown that a combination of bone marrow and (BCP) was effective to repair irradiated bone. However, the origin and role played by each cell type in bone healing still remains unclear. In order to track the grafted cells, the development of an animal model that is immunotolerant to an allograft of bone marrow would be useful. Furthermore, because the immune system interacts with bone turnover, it is of critical importance to demonstrate that immunosuppressive drugs do not interfere with bone repair. After a preliminary study of immunotolerance, cyclosporin-A was chosen to be used in immunosuppressive therapy. Ten rats were included to observe qualitative and quantitative bone repair 8 days and 6 weeks after the creation of bone defects. The defects were filled with an allograft of bone marrow alone or in association with BCP under immunosuppressive treatment (cyclosporin-A). The results showed that there was no significant interaction of cyclosporin-A with osseous regeneration. The use of this new immunotolerant rat model of bone marrow allograft in future studies will provide insight on how the cells within the bone marrow graft contribute to bone healing, especially in irradiated conditions.
    Calcified Tissue International 02/2015; 96(5). DOI:10.1007/s00223-015-9970-z · 3.27 Impact Factor
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    ABSTRACT: Trabecular bone and its micro-architecture are of prime importance for health. Changes of bone micro-architecture are linked to different pathological situations like osteoporosis and begin now to be understood. In a previous paper [12], we started to investigate the relationships between bone and vessels and proposed some indices of characterization for the vessels issued from those used for the bone. Our main objective in this paper is to qualify the classical values used for bone as well as those we proposed for vessels according to different acquisition parameters and for several thresholding methods used to separate bone vessels and background. This study is also based on vessels perfusion by a contrast agent (barium sulfate mixed with gelatin) before euthanasia on rats. Femurs and tibias as well as mandibles were removed after rat's death and were imaged by microCT (Skyscan 1272, Bruker, Belgium) with a resolution ranging from 18 to 3μm. The so obtained images were analyzed with various softwares (NRecon Reconstruction, CtAn, and CtVox from Bruker) in order to calculate bone and vessels micro-architecture parameters (density of bone/blood within the volume), and to know if the results both for bone and vascular micro-architecture are constant along the chosen pixel resolution. The result is clearly negative. We found a very different characterization both for bone and vessels with the 3μm acquisition. Tibia and mandibles bones were also used to show results that can be visually assessed. The largest portions of the vascular tree are orthogonal to the obtained slices of the bone. Therefore, the contrast agent appears as cylinders of various sizes.
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    ABSTRACT: Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles <10 µm is systematically higher in the generic solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened.
    PLoS ONE 12/2014; 9(12):e113991. DOI:10.1371/journal.pone.0113991 · 3.23 Impact Factor
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    ABSTRACT: In the context of bone regeneration in an osteoporotic environment, the present study described the development of an approach based on the use of calcium phosphate (CaP) bone substitutes that can promote new bone formation and locally deliver in situ bisphosphonate (BP), directly at the implantation site. The formulation of a CaP material has been optimized by designing an injectable apatitic cement that (i) hardens in situ despite the presence of BP and (ii) provides immediate mechanical properties adapted to clinical applications in an osteoporotic environment. We developed a large animal model for simulating lumbar vertebroplasty through a two-level lateral corpectomy on L3 and L4 vertebrae presenting a standardized osteopenic bone defect that was filled with cements. Both 2D and 3D analysis of micro-architectural parameters demonstrated that implantation of BP loaded cement in such vertebral defects positively influenced microarchitecture of the adjacent trabecular bone. This biological effect was distance-dependent from the implant, emphasizing the in situ effect of the BP and its release from the cement. As a drug device combination, this BP-containing apatitic cement shows good promise local approach for the prevention of osteoporotic vertebral fractures through percutaneous vertebroplasty procedures.
    Acta Biomaterialia 11/2014; 10(11). DOI:10.1016/j.actbio.2014.07.012 · 6.03 Impact Factor
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    ABSTRACT: The consequences of the treatment of the squamous cell carcinomas of the upper aerodigestive tract (bone removal and external radiation therapy) are constant. Tissue engineering using biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSC) is considered as a promising alternative. We previously demonstrated the efficacy of BCP and total fresh bone marrow (TBM) in regenerating irradiated bone defect. The aim of this study was to know if adding MSC to BCP + TBM mixture could improve the bone formation in irradiated bone defects. Twenty-four Lewis 1A rats received a single dose of 20 Gy to the hind limbs. MSC were sampled from non-irradiated donors and amplified in proliferative, and a part in osteogenic, medium. 3 weeks after, defects were created on femurs and tibias, which were filled with BCP alone, BCP + TBM, BCP + TBM + uncommitted MSC, or BCP + TBM + committed MSC. 3 weeks after, samples were removed and prepared for qualitative and quantitative analysis. The rate of bone ingrowth was significantly higher after implantation of BCP + TBM mixture. The adding of a high concentration of MSC, committed or not, didn't improve the bone regeneration. The association BCP + TBM remains the most efficient material for bone substitution in irradiated areas.
    Journal of Materials Science Materials in Medicine 08/2014; 25(12). DOI:10.1007/s10856-014-5282-5 · 2.59 Impact Factor
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    ABSTRACT: Maintenance of cell survival is essential for proper embryonic development. In the mouse, Notchless homolog 1 (Drosophila) (Nle1) is instrumental for survival of cells of the inner cell mass upon implantation. Here, we analyze the function of Nle1 after implantation using the Meox2tm1(cre)Sor mouse that expresses the Cre recombinase specifically in the epiblast at E5.5. First, we find that NLE1 function is required in epiblast cells, as Nle1-deficient cells are rapidly eliminated. In this report, we also show that the Meox2Cre transgene is active in specific tissues during organogenesis. In particular, we detect high Cre expression in the vertebral column, ribs, limbs and tailbud. We took advantage of this dynamic expression profile to analyze the effects of inducing mosaic deletion of Nle1 in the embryo. We show that Nle1 deletion in this context, results in severe developmental anomalies leading to lethality at birth. Mutant embryos display multiple developmental defects in particular during axial skeletal formation. We also provide evidence that axial defects are due to an increase in apoptotic cell death in the somite at E9.5. These data demonstrate an essential role for Nle1 during organogenesis and in particular during axial development.
    PLoS ONE 05/2014; 9(5):e98507. DOI:10.1371/journal.pone.0098507 · 3.23 Impact Factor
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    ABSTRACT: Micro-CT represents a modality where the quality of CT reconstruction is very high thanks to the acquisition properties. The goal of this paper is to challenge our proposed Mojette discrete reconstruction scheme from real micro-CT data. A first study was done to analyze bone image degradations by lowering the number of projections. A second study analyzes trabecular bone and vessels tree through an animal study. Small vessels are filling trabecular holes with almost the same grey levels as the bone. Therefore vessel detectability that can be achieved from the reconstruction algorithm according to the number of projections is a major issue. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
    Proc. SPIE 9033, Medical Imaging 2014: Physics of Medical Imaging, 90333A; 03/2014
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    ABSTRACT: This study reports on the incorporation of the self-setting polysaccharide derivative hydrogel (silanized-hydroxypropyl methylcellulose, or Si-HPMC) into the formulation of calcium phosphate cements (CPCs) to develop a novel injectable material for bone substitution. The effects of Si-HPMC on the handling properties (injectability, cohesion and setting time) and mechanical properties (Young's modulus, fracture toughness, flexural and compressive strength) of CPCs were systematically studied. It was found that Si-HPMC could endow composite CPC pastes an appealing rheological behavior at the early stage of setting, promoting its application in open bone cavities. Moreover, Si-HPMC made the composite CPC have a good injectability and cohesion, and reduced the setting time. After hardening, Si-HPMC increased the porosity of CPCs, especially the macroporosity as a result of entrapped air bubbles; however it did not compromise but even improve the mechanical properties of composite CPCs, which demonstrates a strong toughening and strengthening effect. In view of the above, the Si-HPMC composite CPC may be particularly promising as bone substitute material for clinic application.
    Acta biomaterialia 03/2014; 10(7). DOI:10.1016/j.actbio.2014.03.009 · 6.03 Impact Factor
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    ABSTRACT: Autologous bone grafting (BG) remains the standard reconstruction strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials, such as biphasic calcium phosphate (BCP), do not yield consistent results when used alone and must then be combined with cells through bone tissue engineering (BTE). In this context, total bone marrow (TBM) and bone marrow-derived mesenchymal stem cells (MSC) are the primary sources of cellular material used with biomaterials. However, several other BTE strategies exist, including the use of growth factors, various scaffolds, and MSC isolated from different tissues. Thus, clinicians might be unsure as to which method offers patients the most benefit. For this reason, the aim of this study was to compare eight clinically relevant BTE methods in an "all-in-one" study. We used a transgenic rat strain expressing green fluorescent protein (GFP), from which BG, TBM, and MSC were harvested. Progenitor cells were then mixed with CaP materials and implanted subcutaneously into nude mice. After eight weeks, bone formation was evaluated by histology and scanning electron microscopy, and GFP-expressing cells were tracked with photon fluorescence microscopy. Bone formation was observed in only four groups. These included CaP materials mixed with BG or TBM, in which abundant de novo bone was formed, and BCP mixed with committed cells grown in two- and three-dimensions, which yielded limited bone formation. Fluorescence microscopy revealed that only the TBM and BG groups were positive for GFP expressing-cells, suggesting that these donor cells were still present in the host and contributed to the formation of bone. Since the TBM-based procedure does not require bone harvest or cell culture techniques, but provides abundant de novo bone formation, we recommend consideration of this strategy for clinical applications.
    PLoS ONE 12/2013; 8(12):e81599. DOI:10.1371/journal.pone.0081599 · 3.23 Impact Factor
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    ABSTRACT: Recently, nutritional and pharmaceutical benefits of pomegranate (PG) have raised a growing scientific interest. Since PG is endowed with anti-inflammatory and antioxidant activities, we hypothesized that it may have beneficial effects on osteoporosis. We used ovariectomized (OVX) mice as a well-described model of postmenopausal osteoporosis to study the influence of PG consumption on bone health. Mice were divided into five groups as following: two control groups sham-operated and ovariectomized (OVX CT) mice fed a standard diet, versus three treated groups OVX mice given a modified diet from the AIN-93G diet, containing 5.7 % of PG lyophilized mashed totum (OVX PGt), or 9.6 % of PG fresh juice (OVX PGj) or 2.9 % of PG lyophilized mashed peel (OVX PGp). As expected, ovariectomy was associated with a decreased femoral bone mineral density (BMD) and impaired bone micro-architecture parameters. Consumption of PGj, PGp, or PGt induced bone-sparing effects in those OVX mice, both on femoral BMD and bone micro-architecture parameters. In addition, PG (whatever the part) up-regulated osteoblast activity and decreased the expression of osteoclast markers, when compared to what was observed in OVX CT animals. Consistent with the data related to bone parameters, PG consumption elicited a lower expression of pro-inflammatory makers and of enzymes involved in ROS generation, whereas the expression of anti-inflammatory markers and anti-oxidant actors was enhanced. These results indicate that all PG parts are effective in preventing the development of bone loss induced by ovariectomy in mice. Such an effect could be partially explained by an improved inflammatory and oxidative status.
    European Journal of Nutrition 11/2013; 53(5). DOI:10.1007/s00394-013-0615-6 · 3.47 Impact Factor
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    ABSTRACT: In the current context of longer life expectancy, the prevalence of osteoporosis is increasingly important. This is why development of new strategies of prevention is highly suitable. Pomegranate seed oil (PSO) and its major component, punicic acid (a conjugated linolenic acid), have potent anti-inflammatory and anti-oxidative properties both in vitro and in vivo, two processes strongly involved in osteoporosis establishment. In this study, we demonstrated that PSO consumption (5% of the diet) improved significantly bone mineral density (240.24±11.85 vs. 203.04±34.19 mg/cm(3)) and prevented trabecular microarchitecture impairment in ovariectomized (OVX) mice C57BL/6J, compared to OVX control animals. Those findings are associated with transcriptional changes in bone tissue, suggesting involvement of both osteoclastogenesis inhibition and osteoblastogenesis improvement. In addition, thanks to an ex vivo experiment, we provided evidence that serum from mice fed PSO (5% by gavage) had the ability to significantly down-regulate the expression of specific osteoclast differentiation markers and RANK-RANKL downstream signaling targets in osteoclast-like cells (RAW264.7) (RANK: negative 0.49-fold vs. control conditions). Moreover, in osteoblast-like cells (MC3T3-E1), it elicited significant increase in alkaline phosphatase activity (+159% at day 7), matrix mineralization (+271% on day 21) and transcriptional levels of major osteoblast lineage markers involving the Wnt/β-catenin signaling pathways. Our data also reveal that PSO inhibited pro-inflammatory factors expression while stimulating anti-inflammatory ones. These results demonstrate that PSO is highly relevant regarding osteoporosis. Indeed, it offers promising alternatives in the design of new strategies in nutritional management of age-related bone complications.
    The Journal of nutritional biochemistry 08/2013; 24(11). DOI:10.1016/j.jnutbio.2013.04.005 · 3.79 Impact Factor

Publication Stats

3k Citations
384.12 Total Impact Points


  • 2007-2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2011-2014
    • French Institute of Health and Medical Research
      • • Laboratory of Osteoarticular and Dental Tissue Engineering
      • • Center of Research in Transplantation and Immunology CRTI
      Lutetia Parisorum, Île-de-France, France
  • 2003-2014
    • Centre Hospitalier Universitaire de Nantes
      Naoned, Pays de la Loire, France
  • 2002-2014
    • University of Nantes
      • • Faculté de Chirurgie Dentaire
      • • Musculoskeltal and Dental Engineering Institute
      Naoned, Pays de la Loire, France
  • 2009
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2004
    • Fraunhofer Institute for High-Speed Dynamics, Ernst-Mach-Institut EMI
      Freiburg, Baden-Württemberg, Germany
  • 1996
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France