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This study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes endothelium-derived epoxyeicosatrienoic acids, plays a role in vascular calcification. The sEH inhibitor trans-4-(4-(3-adamantan-1-yl-ureido)-cyclohexyloxy)-benzoic acid (t-AUCB) potentiated the increase in calcium deposition of rat aortic rings cultured in high-phosphate conditions. This was associated with increased tissue-nonspecific alkaline phosphatase activity and mRNA expression level of the osteochondrogenic marker Runx2. The procalcifying effect of t-AUCB was prevented by mechanical aortic deendothelialization or inhibition of the production and action of epoxyeicosatrienoic acids using the cytochrome P450 inhibitor fluconazole and the antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE), respectively. Similarly, exogenous epoxyeicosatrienoic acids potentiated the calcification of rat aortic rings through a protein kinase A (PKA)-dependent mechanism and of human aortic vascular smooth muscle cells when sEH was inhibited by t-AUCB. Finally, a global gene expression profiling analysis revealed that the mRNA expression level of sEH was decreased in human carotid calcified plaques compared to adjacent lesion-free sites and was inversely correlated with Runx2 expression. These results show that sEH hydrolase plays a protective role against vascular calcification by reducing the bioavailability of epoxyeicosatrienoic acids.
Olivier Varennes; Romuald Mentaverri; Thomas Duflot; Gilles Kauffenstein; Thibaut Objois; Gaëlle Lenglet; Carine Avondo; Christophe Morisseau; Michel Brazier; Saïd Kamel; Isabelle Six; Jeremy Bellien. The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification. International Journal of Molecular Sciences 2020, 21, 1 .
AMA StyleOlivier Varennes, Romuald Mentaverri, Thomas Duflot, Gilles Kauffenstein, Thibaut Objois, Gaëlle Lenglet, Carine Avondo, Christophe Morisseau, Michel Brazier, Saïd Kamel, Isabelle Six, Jeremy Bellien. The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification. International Journal of Molecular Sciences. 2020; 21 (12):1.
Chicago/Turabian StyleOlivier Varennes; Romuald Mentaverri; Thomas Duflot; Gilles Kauffenstein; Thibaut Objois; Gaëlle Lenglet; Carine Avondo; Christophe Morisseau; Michel Brazier; Saïd Kamel; Isabelle Six; Jeremy Bellien. 2020. "The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification." International Journal of Molecular Sciences 21, no. 12: 1.
Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial cells and resident fibroblasts), and monocyte-derived macrophages. Indeed, the production of pro-inflammatory cytokines and oxidative stress by monocyte-derived macrophages is responsible for the osteogenic transformation and mineralization of vascular/valvular cells. However, monocytes/macrophages show the ability to modify their phenotype, and consequently their functions, when facing environmental modifications. This plasticity complicates efforts to understand the pathogenesis of CVC—particularly in a CKD setting, where both uraemic toxins and CKD treatment may affect monocyte/macrophage functions and thereby influence CVC. Here, we review (i) the mechanisms by which each monocyte/macrophage subset either promotes or prevents CVC, and (ii) how both uraemic toxins and CKD therapies might affect these monocyte/macrophage functions.
Lucie Hénaut; Alexandre Candellier; Cédric Boudot; Maria Grissi; Romuald Mentaverri; Gabriel Choukroun; Michel Brazier; Saïd Kamel; Ziad A. Massy. New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease. Toxins 2019, 11, 529 .
AMA StyleLucie Hénaut, Alexandre Candellier, Cédric Boudot, Maria Grissi, Romuald Mentaverri, Gabriel Choukroun, Michel Brazier, Saïd Kamel, Ziad A. Massy. New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease. Toxins. 2019; 11 (9):529.
Chicago/Turabian StyleLucie Hénaut; Alexandre Candellier; Cédric Boudot; Maria Grissi; Romuald Mentaverri; Gabriel Choukroun; Michel Brazier; Saïd Kamel; Ziad A. Massy. 2019. "New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease." Toxins 11, no. 9: 529.
Nephrol Dial Transplant 2017; 32 (5): 870-879. doi: 10.1093/ndt/gfw042
Aurélie Lenglet; Sophie Liabeuf; Najeh El Esper; Sandrine Brisset; Janette Mansour; Anne-Sophie Lemaire-Hurtel; Aurelien Mary; Michel Brazier; Said Kamel; Romuald Mentaverri; Gabriel Choukroun; Albert Fournier; Ziad A. Massy. Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study. Nephrology Dialysis Transplantation 2017, 32, 1597 -1597.
AMA StyleAurélie Lenglet, Sophie Liabeuf, Najeh El Esper, Sandrine Brisset, Janette Mansour, Anne-Sophie Lemaire-Hurtel, Aurelien Mary, Michel Brazier, Said Kamel, Romuald Mentaverri, Gabriel Choukroun, Albert Fournier, Ziad A. Massy. Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study. Nephrology Dialysis Transplantation. 2017; 32 (9):1597-1597.
Chicago/Turabian StyleAurélie Lenglet; Sophie Liabeuf; Najeh El Esper; Sandrine Brisset; Janette Mansour; Anne-Sophie Lemaire-Hurtel; Aurelien Mary; Michel Brazier; Said Kamel; Romuald Mentaverri; Gabriel Choukroun; Albert Fournier; Ziad A. Massy. 2017. "Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study." Nephrology Dialysis Transplantation 32, no. 9: 1597-1597.
Our results indicate that CaSR expression in synovial derived monocytes is higher in osteoarthritis than in inflammatory rheumatisms and that CaSR expression is modulated by the nature of the synovial fluid. Given the role played by monocytes in the pathogenesis of chronic rheumatisms, monocytes could be interesting therapeutic targets via the CaSR.
Alice Séjourné; Cédric Boudot; Thibaut Objois; Patrice Fardellone; Michel Brazier; Isabelle Six; Saïd Kamel; Romuald Mentaverri; Vincent Goeb. Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis. Joint Bone Spine 2017, 84, 175 -181.
AMA StyleAlice Séjourné, Cédric Boudot, Thibaut Objois, Patrice Fardellone, Michel Brazier, Isabelle Six, Saïd Kamel, Romuald Mentaverri, Vincent Goeb. Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis. Joint Bone Spine. 2017; 84 (2):175-181.
Chicago/Turabian StyleAlice Séjourné; Cédric Boudot; Thibaut Objois; Patrice Fardellone; Michel Brazier; Isabelle Six; Saïd Kamel; Romuald Mentaverri; Vincent Goeb. 2017. "Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis." Joint Bone Spine 84, no. 2: 175-181.
Vascular calcification (VC) is a degenerative disease that contributes to cardiovascular morbidity and mortality. A negative relationship has been demonstrated between VC and calcium sensing receptor (CaSR) expression in the vasculature. Of interest, vitamin D response elements, which allow responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are present in the promoters of the CaSR gene. We hypothesized that 1,25(OH)2D3, by modulating CaSR expression in vascular smooth muscle cells (VSMCs), might protect against VC. Human VSMCs were exposed to increasing concentrations of 1,25(OH)2D3 (0.01–10 nmol/L) in noncalcifying (1.8 mmol/L) or procalcifying Ca2+0 condition (5.0 mmol/L). Using quantitative RT-PCR and Western blotting we observed a significant increase in both CaSR mRNA and protein levels after exposure to 1.0 nmol/L 1,25(OH)2D3. This effect was associated with a maximal increase in CaSR expression at the cell surface after 48 hours of 1,25(OH)2D3 treatment, as assessed by flow cytometry. Down-regulation of the vitamin D receptor by small interfering RNA abolished these effects. In the procalcifying condition, 1.0 nmol/L 1,25(OH)2D3 blocked the Ca2+0-induced decrease in total and surface CaSR expression and protected against mineralization. Down-regulation of CaSR expression by CaSR small interfering RNA abolished this protective effect. 1,25(OH)2D3 concentrations of 0.5 and 5.0 nmol/L were also effective, but other (0.01, 0.1, and 10 nmol/L) concentrations did not modify CaSR expression and human VSMC mineralization. In conclusion, these findings suggest that nanomolar concentrations of 1,25(OH)2D3 induce a CaSR-dependent protection against VC. Both lower and higher concentrations are either ineffective or may even promote VC. Whether this also holds true in the clinical setting requires further study.
Aurélien Mary; Lucie Hénaut; Cédric Boudot; Isabelle Six; Michel Brazier; Ziad A. Massy; Tilman B. Drueke; Saïd Kamel; Romuald Mentaverri. Calcitriol Prevents In Vitro Vascular Smooth Muscle Cell Mineralization by Regulating Calcium-Sensing Receptor Expression. Endocrinology 2015, 156, 1965 -1974.
AMA StyleAurélien Mary, Lucie Hénaut, Cédric Boudot, Isabelle Six, Michel Brazier, Ziad A. Massy, Tilman B. Drueke, Saïd Kamel, Romuald Mentaverri. Calcitriol Prevents In Vitro Vascular Smooth Muscle Cell Mineralization by Regulating Calcium-Sensing Receptor Expression. Endocrinology. 2015; 156 (6):1965-1974.
Chicago/Turabian StyleAurélien Mary; Lucie Hénaut; Cédric Boudot; Isabelle Six; Michel Brazier; Ziad A. Massy; Tilman B. Drueke; Saïd Kamel; Romuald Mentaverri. 2015. "Calcitriol Prevents In Vitro Vascular Smooth Muscle Cell Mineralization by Regulating Calcium-Sensing Receptor Expression." Endocrinology 156, no. 6: 1965-1974.
Sophie Liabeuf; Olivier Bourron; Cees Vemeer; Elke Theuwissen; Elke Magdeleyns; Carole Elodie Aubert; Michel Brazier; Romuald Mentaverri; Agnes Hartemann; Ziad A Massy. Erratum: Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein. Cardiovascular Diabetology 2015, 14, 9 .
AMA StyleSophie Liabeuf, Olivier Bourron, Cees Vemeer, Elke Theuwissen, Elke Magdeleyns, Carole Elodie Aubert, Michel Brazier, Romuald Mentaverri, Agnes Hartemann, Ziad A Massy. Erratum: Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein. Cardiovascular Diabetology. 2015; 14 (1):9.
Chicago/Turabian StyleSophie Liabeuf; Olivier Bourron; Cees Vemeer; Elke Theuwissen; Elke Magdeleyns; Carole Elodie Aubert; Michel Brazier; Romuald Mentaverri; Agnes Hartemann; Ziad A Massy. 2015. "Erratum: Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein." Cardiovascular Diabetology 14, no. 1: 9.
Human circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis. This study investigated the potential association between vascular calcification in rheumatoid arthritis (RA) and CaSR expression in circulating monocytes. In this cross-sectional study, 50 RA patients were compared to 25 control subjects matched for age and gender. Isolation of peripheral blood mononuclear cells and flow cytometry analysis were performed to study the surface and total CaSR expression in circulating monocytes. Coronary artery calcium (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography and an association between these scores and the surface and/or total CaSR expression in circulating monocytes in RA patients was investigated. The two groups were similar in terms of age (RA: 60.9 ± 8.3 years, versus controls: 59.6 ± 5.3 years) and gender (RA: 74.0% females versus 72.0% females). We did not find a higher prevalence and greater burden of CAC or AAC in RA patients versus age- and gender-matched controls. When compared with control subjects, RA patients did not exhibit greater total CaSR (101.6% ± 28.8 vs. 99.9% ± 22.0) or surface CaSR (104.6% ± 20.4 vs. 99.9% ± 13.7) expression, but total CaSR expression in circulating monocytes was significantly higher in RA patients with severe CAC (Agatston score ≥200, n = 11) than in patients with mild-to-moderate CAC (1 to 199, n = 21) (P = 0.01). This study demonstrates for the first time that total CaSR expression in human circulating monocytes is increased in RA patients with severe coronary artery calcification.
Julien Paccou; Cédric Boudot; Cédric Renard; Sophie Liabeuf; Said Kamel; Patrice Fardellone; Ziad Massy; Michel Brazier; Romuald Mentaverri. Total calcium-sensing receptor expression in circulating monocytes is increased in rheumatoid arthritis patients with severe coronary artery calcification. Arthritis Research & Therapy 2014, 16, 1 -9.
AMA StyleJulien Paccou, Cédric Boudot, Cédric Renard, Sophie Liabeuf, Said Kamel, Patrice Fardellone, Ziad Massy, Michel Brazier, Romuald Mentaverri. Total calcium-sensing receptor expression in circulating monocytes is increased in rheumatoid arthritis patients with severe coronary artery calcification. Arthritis Research & Therapy. 2014; 16 (4):1-9.
Chicago/Turabian StyleJulien Paccou; Cédric Boudot; Cédric Renard; Sophie Liabeuf; Said Kamel; Patrice Fardellone; Ziad Massy; Michel Brazier; Romuald Mentaverri. 2014. "Total calcium-sensing receptor expression in circulating monocytes is increased in rheumatoid arthritis patients with severe coronary artery calcification." Arthritis Research & Therapy 16, no. 4: 1-9.
Matrix Gla protein (MGP) is an important inhibitor of calcification. The objective of the present study of patients with type 2 diabetes and normal or slightly altered kidney function was to evaluate levels of inactive, dephospho-uncarboxylated MGP(dp-ucMGP) and total uncarboxylated MGP(t-ucMGP) and assess their links with biological and clinical parameters (including peripheral vascular calcification).
Sophie Liabeuf; Bourron Olivier; Cees Vemeer; Elke Theuwissen; Elke Magdeleyns; Carole Elodie Aubert; Michel Brazier; Romuald Mentaverri; Agnes Hartemann; Ziad A Massy. Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein. Cardiovascular Diabetology 2014, 13, 85 -85.
AMA StyleSophie Liabeuf, Bourron Olivier, Cees Vemeer, Elke Theuwissen, Elke Magdeleyns, Carole Elodie Aubert, Michel Brazier, Romuald Mentaverri, Agnes Hartemann, Ziad A Massy. Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein. Cardiovascular Diabetology. 2014; 13 (1):85-85.
Chicago/Turabian StyleSophie Liabeuf; Bourron Olivier; Cees Vemeer; Elke Theuwissen; Elke Magdeleyns; Carole Elodie Aubert; Michel Brazier; Romuald Mentaverri; Agnes Hartemann; Ziad A Massy. 2014. "Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein." Cardiovascular Diabetology 13, no. 1: 85-85.
Vascular calcification is frequent in patients with chronic kidney disease. Osteoprotegerin (OPG, a soluble factor which blocks osteoclast differentiation) has recently been implicated in the genesis of vascular calcification. Given that OPG can bind the pro-apoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we hypothesized that the TRAIL protein is involved in the formation of vascular calcification both in vitro and in vivo. Using an immunohistochemical approach, we evaluated TRAIL and OPG expression on aortic valves slides from non-uremic and uremic wild type and apolipoprotein knockout (Apo E(-/-) ) mice. We also tested the in vitro effects of TRAIL on cultured primary human vascular smooth muscle cells (hVSMC). We further assayed serum soluble TRAIL (sTRAIL) levels in hemodialysis patients and correlated them with vascular calcification scores. Our results demonstrated that: (i) TRAIL and OPG were expressed inside the atheroma plaque in non-uremic ApoE(-/-) mice, but not in wild type mice; and (ii) uremia enhanced the expression levels. TRAIL enhanced the phosphate-induced mineralization of hVSMCs in a dose-dependent manner. In clinical terms, we demonstrated that sTRAIL is depressed in the sera of hemodialysis patients, but was not correlated with vascular calcification. Our results suggest that TRAIL may be involved in the formation of vascular calcification in certain experimental settings; however, its role in chronic kidney disease patients requires further evaluation.
Maud Chasseraud; Sophie Liabeuf; Anaïs Mozar; Romuald Mentaveri; Michel Brazier; Ziad A Massy; Said Kamel. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Vascular Calcification. Therapeutic Apheresis and Dialysis 2011, 15, 140 -146.
AMA StyleMaud Chasseraud, Sophie Liabeuf, Anaïs Mozar, Romuald Mentaveri, Michel Brazier, Ziad A Massy, Said Kamel. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Vascular Calcification. Therapeutic Apheresis and Dialysis. 2011; 15 (2):140-146.
Chicago/Turabian StyleMaud Chasseraud; Sophie Liabeuf; Anaïs Mozar; Romuald Mentaveri; Michel Brazier; Ziad A Massy; Said Kamel. 2011. "Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Vascular Calcification." Therapeutic Apheresis and Dialysis 15, no. 2: 140-146.
Axelle Caudrillier; Romuald Mentaverri; Michel Brazier; Said Kamel; Ziad A Massy. Calcium-sensing receptor as a potential modulator of vascular calcification in chronic kidney disease. Journal of Nephrology 2010, 23, 1 .
AMA StyleAxelle Caudrillier, Romuald Mentaverri, Michel Brazier, Said Kamel, Ziad A Massy. Calcium-sensing receptor as a potential modulator of vascular calcification in chronic kidney disease. Journal of Nephrology. 2010; 23 (1):1.
Chicago/Turabian StyleAxelle Caudrillier; Romuald Mentaverri; Michel Brazier; Said Kamel; Ziad A Massy. 2010. "Calcium-sensing receptor as a potential modulator of vascular calcification in chronic kidney disease." Journal of Nephrology 23, no. 1: 1.
Breast cancer is the most frequent form of cancer in women, with the highest incidence of metastasis to the bone. The reason for the preferential destination to the bone is believed to be due to chemoattractant factors released during bone resorption, which act on the cancer cells facilitating their metastasis. One of the factors released during osteolysis that may mediate breast cancer bone localization is Ca2+. Here, we show that extracellular Ca2+ (Ca2+o) acting via the calcium-sensing receptor (CaSR), greatly promotes the migration of bone-preferring breast cancer cells. In Boyden Chamber and Scratch Wound migration assays, an increase in breast cancer cell migration was observed at 2.5 mM and 5 mM Ca2+o compared to basal levels for three of the four breast cancer cell lines tested. However, a significantly greater migratory response was observed for the highly bone metastatic MDA-MB-231 cells, compared to the MCF7 and T47D, which have a lower metastatic potential in vivo. The BT474 cells, which do not metastasize to the bone, did not respond to elevated concentrations of Ca2+o in the migration assays. Inhibition of either ERK1/2 MAPK or phospholipase Cβ (PLCβ) led to an abolition of the Ca2+o-induced migration, implicating these pathways in the migratory response. Knockdown of the CaSR by siRNA resulted in an inhibition of the Ca2+o-induced migration, demonstrating the involvement of this receptor in the effect. These results suggest that the activation of the CaSR by elevated Ca2+o concentrations, such as those found near resorbing bone, produces an especially strong chemoattractant effect on bone metastatic breast cancer cells toward the Ca2+-rich environment.
Zuzana Saidak; Cedric Boudot; Rachida Abdoune; Laurent Petit; Michel Brazier; Romuald Mentaverri; Said Kamel. Extracellular calcium promotes the migration of breast cancer cells through the activation of the calcium sensing receptor. Experimental Cell Research 2009, 315, 2072 -2080.
AMA StyleZuzana Saidak, Cedric Boudot, Rachida Abdoune, Laurent Petit, Michel Brazier, Romuald Mentaverri, Said Kamel. Extracellular calcium promotes the migration of breast cancer cells through the activation of the calcium sensing receptor. Experimental Cell Research. 2009; 315 (12):2072-2080.
Chicago/Turabian StyleZuzana Saidak; Cedric Boudot; Rachida Abdoune; Laurent Petit; Michel Brazier; Romuald Mentaverri; Said Kamel. 2009. "Extracellular calcium promotes the migration of breast cancer cells through the activation of the calcium sensing receptor." Experimental Cell Research 315, no. 12: 2072-2080.
This study evaluates the effect of the mother-of-pearl (nacre) organic matrix on mammalian osteoclast activity and on cathepsin K protease. Rabbit osteoclasts were cultured on bovine cortical bone slices in the presence of water-soluble molecules extracted from nacre of the pearl oyster Pinctada margaritifera. Osteoclast resorption activity was determined by quantification of the resorption surface area on bovine bone slices. Papain and cathepsin K, B and L inhibition tests were performed in the presence of the nacre water-soluble extracts. The active crude extract was fractionated by dialysis and reversed-phase high-performance liquid chromatography before electrospray mass spectrometry analysis of inhibitory fractions. The water-soluble molecules extracted from nacre decreased bone resorption without jeopardizing osteoclast survival. The hydrolytic activity of cysteine proteinases was reduced when the enzymes were incubated with the nacre water-soluble molecules. Trending towards characterization of the molecules involved, it appears that cathepsin K inhibitors remain in different nacre water-soluble organic matrix subfractions, composed of low molecular weight molecules. Mollusk shell nacre contains molecules capable of reducing osteoclast bone resorption activity by inhibiting cathepsin K, giving a new facet of the bioactivity of nacre as bone biomaterial.
Denis Duplat; Marlène Gallet; Sophie Berland; Arul Marie; Lionel Dubost; Marthe Rousseau; Said Kamel; Christian Milet; Michel Brazier; Evelyne Lopez; Laurent Bedouet. The effect of molecules in mother-of-pearl on the decrease in bone resorption through the inhibition of osteoclast cathepsin K. Biomaterials 2007, 28, 4769 -4778.
AMA StyleDenis Duplat, Marlène Gallet, Sophie Berland, Arul Marie, Lionel Dubost, Marthe Rousseau, Said Kamel, Christian Milet, Michel Brazier, Evelyne Lopez, Laurent Bedouet. The effect of molecules in mother-of-pearl on the decrease in bone resorption through the inhibition of osteoclast cathepsin K. Biomaterials. 2007; 28 (32):4769-4778.
Chicago/Turabian StyleDenis Duplat; Marlène Gallet; Sophie Berland; Arul Marie; Lionel Dubost; Marthe Rousseau; Said Kamel; Christian Milet; Michel Brazier; Evelyne Lopez; Laurent Bedouet. 2007. "The effect of molecules in mother-of-pearl on the decrease in bone resorption through the inhibition of osteoclast cathepsin K." Biomaterials 28, no. 32: 4769-4778.
Flavonoids are micronutrients widely present in food of plant origin. They have been attributed pharmacological properties such as anticancer and prevention of age‐related pathologies. It has been recently hypothesized that flavonoids increase bone mass and prevent osteoporosis. However, little is known about the in vitro effects of flavonoids on osteoclast activities. We investigated the effects of quercetin, one of the most commonly occurring flavonoids, on osteoclast differentiation which is a critical determinant step of in vivo bone resorption. Two in vitro models of osteoclast differentiation were used in this study: a murine one, involving the culture of RAW 264.7 cells in presence of receptor activator of NFκB ligand (RANKL), and a human model consisting of differentiating peripheral blood monocytic cells (PBMC) isolated from peripheral blood in presence of RANKL and macrophage‐colony stimulating factor (M‐CSF). Osteoclastogenesis was assessed by osteoclast‐like number, tartrate resistant acid phosphatase (TRAP) activity, and bone resorbing activity. We showed that quercetin (0.1–10 μM) decreased osteoclastogenesis in a dose dependent manner in both models with significant effects observed at low concentrations, from 1 to 5 μM. The IC50 value was about 1 μM. Analysis of protein–DNA interaction by electrophoretic mobility shift assay (EMSA) performed on RAW cells showed that a pre‐treatment with quercetin inhibited RANKL‐induced nuclear factor kB (NFκB) and activator protein 1 (AP‐1) activation. NFκB and AP‐1 are transcription factors highly involved in osteoclastic differentiation and their inhibition could play an important role in the decrease of osteoclastogenesis observed in the presence of quercetin. In conclusion, the present results demonstrate for the first time that quercetin, a flavonoid characterized by antioxidant activities, is a potent inhibitor of in vitro osteoclastic differentiation, via a mechanism involving NFκB and AP‐1.
Alice Wattel; Said Kamel; Christophe Prouillet; Jean-Pierre Petit; Florence Lorget; Elizabeth Offord; Michel Brazier. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF?B and AP-1. Journal of Cellular Biochemistry 2004, 92, 285 -295.
AMA StyleAlice Wattel, Said Kamel, Christophe Prouillet, Jean-Pierre Petit, Florence Lorget, Elizabeth Offord, Michel Brazier. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF?B and AP-1. Journal of Cellular Biochemistry. 2004; 92 (2):285-295.
Chicago/Turabian StyleAlice Wattel; Said Kamel; Christophe Prouillet; Jean-Pierre Petit; Florence Lorget; Elizabeth Offord; Michel Brazier. 2004. "Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF?B and AP-1." Journal of Cellular Biochemistry 92, no. 2: 285-295.