Metabolism and arthritis
Age-related joint diseases and metabolism
A few years ago, we started to look at the role of tissue interactions in osteoarthritis (OA), a disease initially considered as cartilage-driven. OA is a much more complex disease, with inflammatory mediators released by cartilage, bone and synovium interacting into the joint. Because obesity is a risk factor for OA in non-weight-bearing joints such as the hand, adipokines were suggested to play a role in OA. Starting from our work on the involvement of adipokines in OA, we address the hypothesis of a role of metabolic syndrome in OA progression. Metabolic syndrome-associated OA (MetS-OA) has recently been highlighted among the overall group of OA phenotypes, but the molecular mechanisms underlying the role of MetS in cartilage degradation has been poorly studied. Indeed, studies suggest that OA structural progression may result from altered communication between subchondral bone cells (e.g., osteoblasts, osteocytes) and cartilage cells (chondrocytes) and atheromatous vascular disease of subchondral bone.
In parallel, we have launched a cohort of patients suffering from hand OA going to be followed at least 6 years in order to collect biological, imaging and clincal data to better understand the pathophysiology and the prognosis of this disease.
Four main projects are currently under investigation:
- Identify novel soluble mediators secreted by activated bone cells and acting on chondrocytes.
- Effect of hypertrophic differentiation of chondrocytes on remodelling of the osteochondral junction.
- Role of metabolic syndrome in OA beyond obesity.
- Preclinical/clinical validation of our in vitro or ex vivo discoveries.)
- Primary culture of articular chondrocytes (mouse, human) and costal chondrocytes (mouse), of murine osteoblasts (membrane 3D) and of human synoviocytes
- Control of chondrocyte phenotype (hypertrophic differentiation and fibroblastic dedifferentiation)
- Application of mechanical stress (cartilage explants and bone), Flexercell apparatus
- Bone/cartilage communication model (murine)
- Mesenchymal stem cells (from rat bone marrow
- Cellular analysis (Western-blot, proteolytic activity, ELISA, qRT-PCR, ARN interference, immunocytology)
- Tissue analysis (histology paraffin, immunohistochemistry)
- Experimental model for Osteoarthritis (Mouse)
- Experimental model of tendon repair (Rat)
Fields of interest
Inflammation, osteoarthritis, cartilage, bone, synovial tissue, lipid mediators, cytokines, chondrocyte
Contact infoAddress: UMR-S 938, Bâtiment Kourilsky Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine
Postal code: 75012
Telephone: +33 1 49 28 25 20
Fax: +33 1 49 28 25 13
- Eymard F, Pigenet A, Citadelle D, Flouzat-Lachaniette CH, Poignard A, Benelli C, Berenbaum F, Chevalier X, Houard X
Induction of an Inflammatory and Prodegradative Phenotype in Autologous Fibroblast-like Synoviocytes by the Infrapatellar Fat Pad From Patients With Knee Osteoarthritis
Arthritis Rheumatol. 66, 2165–2174 (2014)
- Bougault C, Priam S, Houard X, Pigenet A, Sudre L, Lories RJ, Jacques C, Berenbaum F
Protective role of frizzled-related protein B on matrix metalloproteinase induction in mouse chondrocytes
Arthritis Res. Ther. 16, R137 (2014)
- Pecchi E, Priam S, Gosset M, Pigenet A, Sudre L, Laiguillon MC, Berenbaum F, Houard X
Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain
Arthritis Res. Ther. 16, R16 (2014)
- Laiguillon MC, Houard X, Bougault C, Gosset M, Nourissat G,Sautet A, Jacques C, Berenbaum F, Sellam J
Expression and function of visfatin (Nampt), an adipokine-enzyme involved in inflammatory pathways of osteoarthritis
Arthritis Res. Ther. 16, R38 (2014)
- Houard X, Goldring MB, Berenbaum F
Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis
Curr. Rheumatol. Rep. 15, 375 (2013)
- Guerquin MJ, Charvet B, Nourissat G, Havis E, Ronsin O, Bonnin MA, Ruggiu M, Olivera-Martinez I, Robert N, Lu Y, Kadler KE, Baumberger T, Doursounian L, Berenbaum F, Duprez D
Transcription factor EGR1 directs tendon differentiation and promotes tendon repair
J Clin Invest. 2013 Aug 1;123(8):3564-76.
- Priam S, Bougault C, Houard X, Gosset M, Salvat C, Berenbaum F, Jacques C
Identification of soluble 14-3-3ε as a new subchondral bone mediator involved in cartilage degradation in osteoarthritis
Arthritis Rheum. 65(7), 1831-1842 (2013)
- Bougault C, Gosset M, Houard X, Salvat C, Godmann L, Pap T, Jacques C, Berenbaum F
Stress-induced cartilage degradation does not depend on the NLRP3 inflammasome in human osteoarthritis and mouse models
Arthritis Rheum. 2012 Dec;64(12):3972-81.
- Jacques C, Holzenberger M, Mladenovic Z, Salvat C, Pecchi E, Berenbaum F, Gosset M
Pro-inflammatory actions of visfatin/Nampt involve regulation of insulin signaling pathway and Nampt enzymatic activity
J Biol Chem. 2012 Apr 27;287(18):15100-8.
- Berenbaum F
Diabetes-induced osteoarthritis: from a new paradigm to a new phenotype
Ann Rheum Dis. 2011 Aug;70(8):1354-6.
- Bijlsma JW, Berenbaum F, Lafeber FP
Osteoarthritis: an update with relevance for clinical practice
The Lancet. 2011 Jun 18;377(9783):2115-26.
- Gosset M, Pigenet A, Salvat C, Berenbaum F, Jacques C
Inhibition of matrix metalloproteinase-3 and -13 synthesis induced by IL-1beta in chondrocytes from mice lacking microsomal prostaglandin E synthase-1
J Immunol. 2010 Nov 15;185(10):6244-52.
- Sellam J, Berenbaum F
The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis
Nat Rev Rheumatol. 2010 Nov;6(11):625-35.
- Blaise R, Mahjoub M, Salvat C, Barbe U, Brou C, Corvol MT, Savouret JF, Rannou F, Berenbaum F, Bausero P
Involvement of the Notch pathway in the regulation of matrix metalloproteinase 13 and the dedifferentiation of articular chondrocytes in murine cartilage
Arthritis Rheum. 2009 Feb;60(2):428-39.
- Gosset M, Berenbaum F, Thirion S, Jacques C
Primary culture and phenotyping of murine chondrocytes
Nature Protoc. 2008;3(8):1253-60.