The effect of adipocytokines on osteoimmunological processes

类风湿性关节炎（RA）是一种以进行性关节破坏为特征的慢性炎症性疾病。脂肪细胞通过分泌脂肪细胞因子影响RA中的炎症过程，而脂肪细胞因子也由滑膜细胞局部产生。脂联素和visfatin/PBEF等脂肪细胞因子刺激RA滑膜成纤维细胞产生基质降解酶和促炎细胞因子。脂联素抑制小鼠破骨细胞并激活成骨细胞，抑制TLR4配体诱导的体外破骨细胞生成，抑制TNF/ rankl诱导的破骨细胞分化。相反，脂联素在抑制OPG的同时诱导成骨细胞的RANKL。该研究的目的是鉴定和靶向脂肪细胞因子或脂肪细胞因子异构体导致骨重塑。因此，脂肪细胞因子的分布，它们的异构体，受体和脂肪因子表达细胞类型在骨吸收部位将被检查。分析脂肪细胞因子及其同型体对破骨细胞的影响将集中在RA的炎症和骨吸收因素上。未知的脂肪因子介导途径和炎症过程影响骨吸收和脂肪因子介导的抑制机制将在体外阐明和研究，并在已建立的RA动物模型中进行翻译。

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.