The effect of adipocytokines on osteoimmunological processes

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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction. Adipocytes influence the inflammatory processes active in RA by secreting adipocytokines, which are also produced locally by synovial cells. Adipocytokines such as adiponectin and visfatin/PBEF stimulate the production of matrix-degrading enzymes and pro-inflammatory cytokines by RA synovial fibroblasts. Adiponectin suppresses osteoclasts and activates osteoblasts in mice, inhibits TLR4 ligand-induced osteoclastogenesis in vitro and inhibits TNF/RANKL-induced osteoclast differentiation. In contrast, adiponectin induces RANKL in osteoblasts while inhibiting OPG. The aim of the study is to identify and target adipocytokines or adipocytokine isoforms leading to bone remodelling. Therefore, the distribution of adipocytokines, their isoforms, receptors and adipokine expressing cell types at sites of bone resorption will be examined. Analysis of the effects of adipocytokines and their isoforms on osteoclasts will focus on factors of inflammation and bone resorption in RA. Unknown adipokine-mediated pathways and inflammatory processes influencing bone resorption and the inhibition of the adipokine-mediated mechanisms will be elucidated and investigated in vitro as well as translational in established animal models of RA.