代谢性骨性关节炎分子机制研究进展

传统观点认为骨性关节炎(osteoarthritis,OA)与衰老、创伤等因素有关,但越来越多的流行病学及生物学证据表明该病的发生与代谢综合征(metabolic syndrome,Met S)及其各组分等关系密切。本文将对该疾病的流行病学及基础研究进行综述,着重阐述其发生发展的分子生物学机制。其中,肥胖能引起脂肪细胞因子水平的异常,使关节内炎症因子和蛋白水解酶增多;高血糖导致的氧化应激、线粒体功能障碍、晚期糖基化终末产物堆积,使软骨细胞代谢稳态被打破;脂代谢异常造成的关节内炎症水平升高、细胞毒性增加、软骨细胞自噬活动减少;高血压使软骨下骨血流减少,使软骨下骨与软骨之间的生物学交流受到影响;"炎性衰老"不但是高血压与骨性关节炎共同的发病机制,也是二者相互影响的关键环节;某些微小RNA能对一些炎症因子,蛋白水解酶的表达进行调控,因而也在骨性关节炎的病理进程中起到了重要作用。本文通过对代谢性骨关节炎相关分子机制的研究,旨在为改善骨性关节炎的防治现状提供新靶点。

Metabolic osteoarthritis: The recent progress in molecular mechanism

Aging, together with injury, is among the common risk factors for osteoarthritis (OA). Evidences from both epidemiological and biological studies support the closed relation between OA and metabolic syndrome. The present review summarizes the related epidemiologic and fundamental researches of metabolic OA, highlighting several molecular mechanisms contributing to the genesis and development of OA. Obesity-related metabolic factors contribute to OA development by increasing adipokines and inducing pro-inflammatory cytokines as well as proteolyses. Excessive amount of glucose may disrupt chondrocyte homeostasis associating with oxidative stress, mitochondrion dysfunction, and accumulating of AGEs. Dyslipidemia can induce active inflammation, increase cell toxicity, and decrease autophagy. Hypertension and atherosclerosis induce the reduction of bone blood flow affecting the biological exchange between cartilage and bone. Inflammaging is not only the common pathogenesis of hypertension and osteoarthritis, but also the key link of the interaction between them. Some microRNAs can regulate the expression of some inflammatory cytokines and degradative enzymes, so that play an important role in the development of osteoarthritis. The purpose of this narrative review is to summarize the mechanism of metabolic osteoarthritis for proposing a potential target for modifying metabolic OA.