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Dive into the research topics where Brigitte Baroukh is active.

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Featured researches published by Brigitte Baroukh.


Bone | 1999

Chemical Sympathectomy Impairs Bone Resorption in Rats: A Role for the Sympathetic System on Bone Metabolism

Marc Cherruau; P Facchinetti; Brigitte Baroukh; Jean-Louis Saffar

The possibility that the nervous system may control bone metabolism has been raised, as neuromediators physiologically conveyed by sympathetic fibers (eg, vasoactive intestinal peptide) influence bone resorption in vitro. In this study, the sympathetic system was inactivated by treating rats with guanethidine (40 mg/kg/day), a sympathetic neurotoxic, for 21 days, after which a wave of osteoclastic resorption was induced along the mandibular buccal cortex. The effects of denervation were assessed 4 days later (corresponding to the peak of resorption in this model). The rats exhibited ptosis soon after starting guanethidine, proving the success of the sympathectomy. This was associated with a significant increase in calcitonin gene-related peptide- (+54%, p < 0.02) and substance P-immunoreactive sensory fibers (+29%,p < 0.02), a known effect of sympathectomy. For the quantitation of the bone parameters, the study zone was divided into a juxta-osseous alkaline phosphatase-positive osteogenic compartment and a nonosteogenic compartment. In the osteogenic compartment, the resorption surface was reduced by 56% (p < 0.001) in the treated animals, together with a fall in the number of osteoclasts (-25%,p < 0.05) and impaired osteoclast access to the bone surface. Tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear preosteoclasts were found only in this compartment; they were reduced by 43% (p < 0.05) by the sympathectomy. No change in non-specific esterase (NSE)+ osteoclast precursors was found. In the nonosteogenic compartment, vasodilation was the only effect of sympathectomy (+80%,p < 0.05); in particular, the number of NSE+ cells was not modified. Our results indicate that: (1) interactions of NSE+ precursors with osteogenic cells are required for their differentiation into TRAP+ preosteoclasts; (2) the sympathetic nervous system is not involved in osteoclast precursor recruitment; but (3) has a significant effect on resorption by inhibiting preosteoclast differentiation and disturbing osteoclast activation. These data suggest that depletion of sympathetic mediators may disturb osteogenic cell-mediated osteoclast differentiation.


Bone | 2009

Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation?

Philippe Lesclous; Semaan Abi Najm; Jean-Pierre Carrel; Brigitte Baroukh; Tommaso Lombardi; Jean-Pierre Willi; René Rizzoli; Jean-Louis Saffar; Jacky Samson

Osteonecrosis of the jaw (ONJ) can be associated with nitrogen-containing bisphosphonates (NBPs) therapy. Various mechanisms of NBP-associated ONJ have been proposed and there is currently no consensus of the underlying pathogenesis. The detailed medical and dental histories of 30 ONJ patients treated with NBPs for malignant diseases (24) or osteoporosis (6) were analyzed. The necrotic bone was resected and analyzed histologically after demineralization. In 10 patients the perinecrotic bone was also resected and processed without demineralization. Alveolar bone samples from 5 healthy patients were used as controls. In 14 ONJ patients, serial technetium-99m-methylene diphosphonate scintigraphic scans were also available and confronted to the other data. Strong radionuclide uptake was detected in some patients several months before clinical diagnosis of ONJ. The medullary spaces of the necrotic bone were filled with bacterial aggregates. In the perinecrotic bone, the bacteria-free bone marrow characteristically showed an inflammatory reaction. The number of medullary inflammatory cells taken as an index of inflammation allowed us to discriminate two inflammation grades in the ONJ samples. Low-grade inflammation, characterized by marrow fibrosis and low inflammatory cells infiltration, increased numbers of TRAP(+) mono- and multineacleated cells was seen in patients with bone exposure<2 cm(2). High-grade inflammation, associated with larger lesions, showed amounts of tartrate-resistant acid phosphatase(+)/calcitonin receptor(-) mono- and multinucleated cells, osteocyte apoptosis, hypervascularization and high inflammatory cell infiltration. The clinical extent of ONJ was statistically linked to the numbers of inflammatory cell. Taken together these data suggest that bone necrosis precedes clinical onset and is an inflammation-associated process. We hypothesize that from an initial focus, bone damage spreads centrifugally, both deeper into the jaw and towards the mucosa before the oral bone exposure and the clinical diagnosis of ONJ.


Journal of Dental Research | 2012

Effect of a Calcium-silicate-based Restorative Cement on Pulp Repair

X.V. Tran; Caroline Gorin; C. Willig; Brigitte Baroukh; B. Pellat; Franck Decup; S. Opsahl Vital; Catherine Chaussain; T. Boukpessi

In cases of pulp injury, capping materials are used to enhance tertiary dentin formation; Ca(OH)2 and MTA are the current gold standards. The aim of this study was to evaluate the capacity of a new calcium-silicate-based restorative cement to induce pulp healing in a rat pulp injury model. For that purpose, cavities with mechanical pulp exposure were prepared on maxillary first molars of 27 six-week-old male rats, and damaged pulps were capped with either the new calcium-silicate-based restorative cement (Biodentine), MTA, or Ca(OH)2. Cavities were sealed with glass-ionomer cement, and the repair process was assessed at several time-points. At day 7, our results showed that both the evaluated cement and MTA induced cell proliferation and formation of mineralization foci, which were strongly positive for osteopontin. At longer time-points, we observed the formation of a homogeneous dentin bridge at the injury site, secreted by cells displaying an odontoblastic phenotype. In contrast, the reparative tissue induced by Ca(OH)2 showed porous organization, suggesting a reparative process different from those induced by calcium silicate cements. Analysis of these data suggests that the evaluated cement can be used for direct pulp-capping.


American Journal of Pathology | 2009

Histamine Promotes Osteoclastogenesis through the Differential Expression of Histamine Receptors on Osteoclasts and Osteoblasts

Martin Biosse-Duplan; Brigitte Baroukh; Michel Dy; Marie-Christine de Vernejoul; Jean-Louis Saffar

In addition to the numerous roles of histamine in both the immune and nervous systems, previous studies have suggested that this bioamine might also be involved in bone metabolism. Following our observations of impaired bone resorption in ovariectomized rats after histamine receptor antagonist treatment, we focused in this study on osteoclasts and osteoclast precursors. We looked for a direct action of histamine on these cells using both in vivo and in vitro approaches. In vivo, we triggered a remodeling sequence in rat mandibular bone and treated the animals with either histamine or histamine receptor antagonists. Histamine was shown to increase the number of osteoclasts and osteoclast precursors whereas antagonists of histamine receptor-1 and -2 decreased both osteoclast recruitment and resorption. In vitro, spleen cells from histamine-deficient mice were treated with receptor activator for nuclear factor kappa B ligand and macrophage colony stimulating factor, giving rise to both reduced numbers of osteoclasts and decreased resorption on dentin slices. Histamine enhanced resorption in these cultures in a dose-dependent manner. In addition, we identified osteoclast precursors as a source of histamine. In contrast, histamine increased the receptor activator for nuclear factor kappa B ligand/osteoprotegerin ratio in primary osteoblasts that did not secrete histamine. We observed a differential expression of histamine receptor-1 and -2 mRNAs in both primary osteoclasts and osteoblasts, confirming their functional roles with selective antagonists. Thus, histamine acts directly on osteoclasts, osteoclast precursors, and osteoblasts, promoting osteoclastogenesis through autocrine/paracrine mechanisms.


PLOS ONE | 2013

MEPE-derived ASARM peptide inhibits odontogenic differentiation of dental pulp stem cells and impairs mineralization in tooth models of X-linked hypophosphatemia.

Benjamin Salmon; Claire Bardet; Mayssam Khaddam; Jiar Naji; Benjamin R. Coyac; Brigitte Baroukh; Franck Letourneur; Julie Lesieur; Franck Decup; Dominique Le Denmat; Antonino Nicoletti; Anne Poliard; Peter S. N. Rowe; Eric Huet; Sibylle Opsahl Vital; Agnès Linglart; Marc D. McKee; Catherine Chaussain

Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) cause X-linked familial hypophosphatemic rickets (XLH), a disorder having severe bone and tooth dentin mineralization defects. The absence of functional PHEX leads to abnormal accumulation of ASARM (acidic serine- and aspartate-rich motif) peptide − a substrate for PHEX and a strong inhibitor of mineralization − derived from MEPE (matrix extracellular phosphoglycoprotein) and other matrix proteins. MEPE-derived ASARM peptide accumulates in tooth dentin of XLH patients where it may impair dentinogenesis. Here, we investigated the effects of ASARM peptides in vitro and in vivo on odontoblast differentiation and matrix mineralization. Dental pulp stem cells from human exfoliated deciduous teeth (SHEDs) were seeded into a 3D collagen scaffold, and induced towards odontogenic differentiation. Cultures were treated with synthetic ASARM peptides (phosphorylated and nonphosphorylated) derived from the human MEPE sequence. Phosphorylated ASARM peptide inhibited SHED differentiation in vitro, with no mineralized nodule formation, decreased odontoblast marker expression, and upregulated MEPE expression. Phosphorylated ASARM peptide implanted in a rat molar pulp injury model impaired reparative dentin formation and mineralization, with increased MEPE immunohistochemical staining. In conclusion, using complementary models to study tooth dentin defects observed in XLH, we demonstrate that the MEPE-derived ASARM peptide inhibits both odontogenic differentiation and matrix mineralization, while increasing MEPE expression. These results contribute to a partial mechanistic explanation of XLH pathogenesis: direct inhibition of mineralization by ASARM peptide leads to the mineralization defects in XLH teeth. This process appears to be positively reinforced by the increased MEPE expression induced by ASARM. The MEPE-ASARM system can therefore be considered as a potential therapeutic target.


Bone | 2000

Osteoclasts differentiate from resident precursors in an in vivo model of synchronized resorption : A temporal and spatial study in rats

Brigitte Baroukh; Marc Cherruau; C Dobigny; D. Guez; Jean-Louis Saffar

Osteoclasts differentiate from mononucleated precursors expressing monocyte markers, which gradually evolve to preosteoclasts expressing the osteoclast phenotype. Although the role of osteogenic cells in these changes has been well documented in vitro, their contribution in vivo has not been established. In this study, a synchronized wave of resorption was activated along the mandibular periosteum. The periosteum adjacent to the bone surface studied was separated by a computer-assisted technique into an osteogenic alkaline phosphatase-positive compartment and an outer nonosteogenic compartment. Specific markers (nonspecific esterase [NSE], tartrate-resistant acid phosphatase [TRAP], and ED1 antibody, a marker of the monocyte-macrophage lineage) were used to follow osteoclast differentiation quantitatively as a function of time after activation of resorption, from day 0 to day 4 (peak of resorption in this model). Local cell proliferation was assessed in parallel. Between day 0 and day 3, the thickness of the osteogenic compartment decreased by 50% (p < 0.0002). In the osteogenic compartment, proliferating cell numbers fell by 80% at 12 day, NSE(+) cells (located farthest from the bone surface) increased 3. 9-fold on day 4 vs. day 0 (p < 0.005), ED1(+) cells decreased between day 0 and day 2 (p < 0.02) before returning to their initial value, and TRAP(+) cells increased 2.7-fold between day 1 and day 3 (p < 0.0005). Resorption was absent in the site studied on day 0, but on day 4 there were 20.5 osteoclast nuclei per millimeter of bone surface. The cell ratio changed from 30.3 NSE(+) and ED1(+) (some of which were also TRAP(+)) cells per millimeter on day 0 to 37.6 mononucleated cells plus 20.5 osteoclast nuclei on day 4. In the nonosteogenic compartment, an entry of ED1(+)/NSE(-) was observed on 12 day (+23 cells, p < 0.02 vs. day 0). This was followed by a return of ED1(+) cell numbers to the control level on day 1, and a transient increase in NSE(+) cells (+47% on day 2 vs. day 1, p < 0.02). TRAP(+) cells were never seen in this compartment. Proliferating cell numbers did not change throughout the study. Our results strongly suggest that the osteoclasts present on day 4 differentiated from the pool of TRAP(+), ED1(+), and NSE(+) cells present at the site on day 0. The osteogenic compartment was gradually replenished by cells migrating from the nonosteogenic compartment, which was supplemented by ED1(+) cells recruited from the circulation early after activation. Moreover, osteogenic cells appeared to be as crucial in vivo for the acquisition of the TRAP phenotype as previously shown in vitro.


Experimental Physiology | 2000

Effects of Capsaicin‐Induced Sensory Denervation on Osteoclastic Resorption in Adult Rats

C. Adam; A. Llorens; Brigitte Baroukh; M. Cherruau; Jean-Louis Saffar

Many recent findings suggest that the nervous system has efferent effects on bone. A putative role of the sensory innervation has been assessed by using a synchronised rat model of bone resorption after treating adult animals with the neurotoxin capsaicin. Fourteen days after capsaicin treatment (50 mg kg−1) the right maxillary molars were extracted to activate a wave of resorption along the mandibular cortex. The rats were killed 4 days later (i.e. at the peak of resorption in this model), and their right mandibles were processed for histometric evaluation of resorption along the cortex and of calcitonin gene‐related peptide (CGRP)‐ and substance P (SP)‐immunoreactive (IR) fibres in the dental pulp. CGRP‐IR and SP‐IR fibres were significantly reduced in numbers by the capsaicin treatment (by 58 and 49%, respectively), confirming the success of sensory denervation. The resorption surface was significantly reduced (P < 0.005) versus the sham‐treated animals. Although the size of the osteoclast population recruited in the site was not modified, the number of actively resorbing osteoclasts was significantly reduced (P < 0.03). However, the activity of the resorbing cells was not modified. Non‐specific esterase‐positive osteoclast precursors were also significantly few after capsaicin treatment. These data show that the sensory nervous system is involved in the control of bone resorption at two different levels: (1) in the recruitment of osteoclast precursors, and (2) in regulating the access of recruited cells to the bone surface.


Experimental Physiology | 2006

Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats

Ph. Lesclous; F. Schramm; S. Gallina; Brigitte Baroukh; D. Guez; Jean-Louis Saffar

Short‐term studies have shown that histamine is involved, via its H2 receptors (H2R), in the mediator network regulating trabecular bone loss in long bones of ovariectomized (OVX) rats. It is not known whether this effect of histamine persists over time or involves other skeletal sites. In this study, rats were maintained for 6 months postOVX and treated daily with saline or famotidine (10 mg kg−1), an H2R antagonist. At the end of the experimental period, femur trabecular bone mass was markedly decreased in OVX rats, whether or not they were treated with famotidine. In contrast, in the fourth lumbar vertebra, where bone loss starts later than in the femur, famotidine treatment attenuated the decline in trabecular bone volume, protected the trabecular architecture, maintained the thickness of the cortices and reduced the numbers of osteoclasts and tartrate‐resistant acid phosphatase‐positive preosteoclasts, whereas it had no influence on bone formation parameters. In vertebral bone marrow of OVX rats, the numbers of mast cells (MCs) and non‐MC histamine‐producing cells increased, while famotidine treatment significantly diminished both cell populations. These data show that H2R antagonism does not protect trabecular bone mass in the long term, and that short‐term protection involves all bones. Histamine is involved during the early phase of strong osteoclastic resorption but not during the late phase of slower resorption, suggesting that different mediator networks control the two phases of destruction. Histamine would be part of the network mediating the early phase.


Journal of Bone and Mineral Research | 2016

Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.

Claire Bardet; Frédéric Courson; Yong Wu; Mayssam Khaddam; Benjamin Salmon; Sandy Ribes; Julia Thumfart; Paulo Marcio Yamaguti; Gaël Y. Rochefort; Marie-Lucile Figueres; Tilman Breiderhoff; Alejandro Garcia-Castaño; Benoît Vallée; Dominique Le Denmat; Brigitte Baroukh; Thomas Guilbert; Alain Schmitt; Jean-Marc Massé; Dominique Bazin; Georg Lorenz; Maria Morawietz; Jianghui Hou; Patricia Carvalho-Lobato; María Cristina Manzanares; Jean-Christophe Fricain; Deborah Talmud; Renato Demontis; Francisco de Assis Rocha Neves; Delphine Zenaty; Ariane Berdal

Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.


Bone | 2011

Different sympathetic pathways control the metabolism of distinct bone envelopes

Caroline Bataille; Cédric Mauprivez; E. Hay; Brigitte Baroukh; Adrian Brun; Catherine Chaussain; Pierre J. Marie; Jean-Louis Saffar; Marc Cherruau

Bone remodeling, the mechanism that modulates bone mass adaptation, is controlled by the sympathetic nervous system through the catecholaminergic pathway. However, resorption in the mandible periosteum envelope is associated with cholinergic Vasoactive Intestinal Peptide (VIP)-positive nerve fibers sensitive to sympathetic neurotoxics, suggesting that different sympathetic pathways may control distinct bone envelopes. In this study, we assessed the role of distinct sympathetic pathways on rat femur and mandible envelopes. To this goal, adult male Wistar rats were chemically sympathectomized or treated with agonists/antagonists of the catecholaminergic and cholinergic pathways; femora and mandibles were sampled. Histomorphometric analysis showed that sympathectomy decreased the number of preosteoclasts and RANKL-expressing osteoblasts in mandible periosteum but had no effect on femur trabecular bone. In contrast, pharmacological stimulation or repression of the catecholaminergic cell receptors impacted the femur trabecular bone and mandible endosteal retromolar zone. VIP treatment of sympathectomized rats rescued the disturbances of the mandible periosteum and alveolar wall whereas the cholinergic pathway had no effect on the catecholaminergic-dependent envelopes. We also found that VIP receptor-1 was weakly expressed in periosteal osteoblasts in the mandible and was increased by VIP treatment, whereas osteoblasts of the retromolar envelope that was innervated only by tyrosine hydroxylase-immunoreactive fibers, constitutively expressed beta-2 adrenergic receptors. These data highlight the complexity of the sympathetic control of bone metabolism. Both the embryological origin of the bone (endochondral for the femur, membranous for the mandibular periosteum and the socket wall) and environmental factors specific to the innervated envelope may influence the phenotype of the sympathetic innervation. We suggest that an origin-dependent imprint of bone cells through osteoblast-nerve interactions determines the type of autonomous system innervating a particular bone envelope.

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Jean-Louis Saffar

Paris Descartes University

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Annie Llorens

Paris Descartes University

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Marc Cherruau

Paris Descartes University

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Claire Bardet

Paris Descartes University

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Benjamin R. Coyac

Paris Descartes University

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Benjamin Salmon

Paris Descartes University

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Julie Lesieur

Paris Descartes University

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Marjolaine Gosset

Paris Descartes University

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