DiMIMP-Rheumatology Unit, University of Bari, Italy.
Curr Drug Targets. 2010 May;11(5):586-98. doi: 10.2174/138945010791011857.
Obesity is one of the main risk factors for osteoarthritis (OA). For many years the association of obesity and OA has been simply attributed to the effects of overload on weight-bearing joints, and epidemiological surveys have shown a strict correlation between an increased body mass index and the severity of knee or hip OA, as well as some relief of pain and disability following weight loss. Instead, there is now a growing body of evidence that obesity is a complex syndrome in which an abnormal activation of neuroendocrine and pro-inflammatory pathways leads to an altered control of food intake, fat expansion and metabolic changes. Activated white adipose tissue increases the synthesis of pro-inflammatory cytokines, such as IL-6, IL-1, IL-8, TNFalpha, IL-18, while regulatory cytokines, such as IL-10, are decreased. Adipocytes also produce peculiar cytokines, namely adipokines, that exert multiple effects, being capable of promoting synovial inflammation, cartilage degrading enzymes, and bone matrix remodeling. Furthermore, pro-inflammatory cytokines stimulate adipocytes to synthesize neuropeptides, such as substance P and nerve growth factor, that have been shown to be critical in regulating both the appetite and cartilage homeostasis. In this scenario, where the influence of obesity on OA stems from a complex interaction of genetic, metabolic, neuroendocrine, and biomechanical factors, there may be various different potential targets for OA therapy.
肥胖是骨关节炎（OA）的主要危险因素之一。多年来，肥胖与 OA 的关联仅仅归因于负荷关节的超负荷影响，流行病学调查显示，体重指数增加与膝关节或髋关节 OA 的严重程度以及减肥后疼痛和残疾的缓解之间存在严格的相关性。相反，现在越来越多的证据表明，肥胖是一种复杂的综合征，其中神经内分泌和促炎途径的异常激活导致食物摄入、脂肪扩张和代谢变化的控制失调。活化的白色脂肪组织增加促炎细胞因子的合成，如 IL-6、IL-1、IL-8、TNFalpha、IL-18，而调节细胞因子，如 IL-10，则减少。脂肪细胞还产生特殊的细胞因子，即脂肪因子，发挥多种作用，能够促进滑膜炎症、软骨降解酶和骨基质重塑。此外，促炎细胞因子刺激脂肪细胞合成神经肽，如 P 物质和神经生长因子，这些神经肽已被证明在调节食欲和软骨稳态方面至关重要。在这种情况下，肥胖对 OA 的影响源于遗传、代谢、神经内分泌和生物力学因素的复杂相互作用，OA 治疗可能有多种不同的潜在靶点。
