Francis Berenbaum

Inflammation and joint diseases related to ageing Paris UR4/ Bertrand Friguet Université Paris 06 (Université Pierre et Marie Curie) Our team associates physiologists, cell biologists, biochemists, and clinicians devoted to the physiological and biological understanding of osteoarthritis, particularly by exploring the role of inflammation, mechanical stress and bone/cartilage/synovial tissue communication in this disease. Research brief Our team “Inflammation and Joint Diseases related to Ageing” has been interested for several years in the physiopathology of osteoarthritis. In the past, the role of prostaglandins and of the arachidonic acid cascade have been extensively investigated in joint tissues. For these objectives, we have developed cellular tools (primary culture of human, rabbit and murine articular and costal chondrocytes, osteoblasts, synoviocytes and mesenchymal cells, alginate-embedded chondrocytes) and tissue (explants of cartilage subjected to compression, biobank of osteoarthritic human tissues) which, coupled to biochemical, molecular analyses and imaging, allow to investigate various research projects. We now focus our projects on the relationship between osteoarthritis and metabolic diseases. The link between osteoarthritis and obesity has been studied by using compressive stress (we have a specific tool dedicated to the assessment of compressive and stretch stress), and by looking at the role of adipokines, with a special interest on visfatin/NAMPT/PBEF. Four main projects are currently under investigation: 1 - Influence of mechanical stress on bone/cartilage communication 2 - Consequences of the hypertrophic differentiation of the chondrocytes on the subchondral bone plate remodelling. 3 - Pro-inflammatory lipid mediators and osteoarthritis 4 - Contribution of the mesenchymal stem cells in tendon repair (experimental rat model of tendon repair validated by our team) and on cartilage metabolism Methodologies used - 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 - 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 in vivo model for Osteoarthritis (Mouse) - Experimental in vivo model of tendon repair (Rat) Publications Sellam J and Berenbaum F. The role of synovitis in osteoarthritis. Nat Rev Rheum, 2010 (in Press).

Gabay O, Sanchez C, Salvat C, Chevy F, Breton M, Nourissat G, Wolf C, Jacques C and F . Berenbaum F. Stigmasterol: a phytosterol with potential anti-osteoarthritic properties. Osteoarthritis Cartilage. 2010;18(1):106-16. 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;60(2):428-39.

Sanchez C, Gabay O, Salvat C, Henrotin YE, Berenbaum F. Mechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts. Osteoarthritis Cartilage. 2009;17(4):473-81. Gosset M, Berenbaum F, Salvat C, Sautet A, Pigenet A, Tahiri K, Jacques C. Crucial role of visfatin/pre-B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum. 2008;58(5):1399-409. Gosset M, Berenbaum F, Thirion S, Jacques C. Primary culture and phenotyping of murine chondrocytes. Nat Protoc. 2008;3(8):1253-60. Jacques C, Recklies AD, Levy A, Berenbaum. HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II collagen expressions. Osteoarthritis Cartilage. 2007;15(2):138-46. ITMO Circulation, Metabolism, Nutrition

Key facts • Team: Researchers: 4 Technicians: 2 PhD students: 2 Postdoc fellows: 1 • Translational approaches: Patents: 1 Clinical research grants: 2 Industry partners: 2 • International research links: Europe, United States

Keywords • Cartilage • osteoarthritis • bone • prostaglandins • cytokine • adipokine • mechanical stress • differentiation • In vitro primary culture • In vivo model • molecular biology • cellular biology

Biological resources • Human, mouse, rabbit and rat primary culture (articular chondrocyte, costal chondrocyte, osteoblasts) •Human synoviocytes •Human OA library (histology, biochemistry) •osteoarthritis mouse model •rat model of tendon repair Contact: Francis Berenbaum

francis.berenbaum@sat.aphp.fr

Cartilage explants Compression model