摘要
Abstract
Osteoarthritis(OA)is a leading cause of disability worldwide,and the understanding of its pathogenesis is undergoing a paradigm shift from a simple"wear-and-tear"disease to a metabolic and low-grade inflammatory disorder.The gut microbiota,as a crucial regulator of host T helper 17(Th17)cells,exhibits complex bidirectional modulatory characteristics.On one hand,microbial metabolites(such as short-chain fatty acids,tryptophan metabolites,and secondary bile acids)help maintain the balance between Th17 cells and regulatory T(Treg)cells,thereby exerting anti-inflammatory and protective effects.These effects are mediated through epigenetic modifications,such as inhibition of histone deacetylase(HDAC),and activation of specific receptors including G-protein-coupled receptor 43(GPR43),aryl hydrocarbon receptor(AHR),and G-protein-coupled bile acid receptor 1(GPBAR1,also known as TGR5).On the other hand,structural components of the microbiota(such as lipopolysaccharides and bacterial extracellular vesicles)activate pro-inflammatory pathways via pattern recognition receptors,thereby promoting Th17 cell differentiation.Further studies have shown that gut-derived Th17 cells and their effector cytokine cytokine interleukin-17(IL-17)serve as a pivotal link connecting gut dysbiosis and joint pathology.After migrating to the joints,Th17 cells and IL-17 act as inflammatory"amplifiers".They not only induce synovial fibroblast activation and inflammatory cascades,but also directly drive cartilage matrix degradation,senescence,and ferroptosis,while promoting abnormal subchondral bone remodelling,ultimately leading to comprehensive destruction of the joint structure.This review aims to summarize the role of the"gut microbiota-Th17/IL-17 immune"axis in the pathogenesis and progression of OA,as well as the related molecular mechanisms.Elucidating the underlying molecular mechanisms of this axis holds promise for providing novel strategies for OA treatment targeting the gut microbiota.关键词
骨关节炎/肠道菌群/白细胞介素-17/17型辅助性T细胞Key words
osteoarthritis/gut microbiota/interleukin-17(IL-17)/T helper 17(Th17)cell分类
医药卫生
