文献类型：期刊文献

英文题名：Revisiting osteoarthritis pathogenesis through the lens of cGAS-STING: Mitochondrial damage, pyroptosis, and inflammatory cascades

作者：Hu, Kangyi[1];Lan, Yuxin[1];Song, Ting[1];Song, Yongjia[1];Song, Min[1]

第一作者：Hu, Kangyi

通信作者：Song, YJ[1];Song, M[1]

机构：[1]Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学中医临床学院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China.|[10735ccd4a8840d96ab71]甘肃中医药大学中医临床学院;[10735]甘肃中医药大学;

年份：2026

卷号：56

外文期刊名：JOURNAL OF ORTHOPAEDIC TRANSLATION

收录：;Scopus(收录号：2-s2.0-105025945849);WOS:【SCI-EXPANDED(收录号:WOS:001716743700001)】；

基金：The work was supported by Gansu University of Chinese Medicine to introduce a talent research start-up fund (2024YJRC-09) ; The 2024 Gansu Basic Research Program-Natural Science Funds-Youth Science and Technology Fund (24JRRA567) ; The 2023 Gansu University of Chinese Medicine Scientific Research and Innovation Fund Project (2023KCYB-14) ; Gansu Province Youth Talent -Individual Project (2025QNGR09)

语种：英文

外文关键词：Osteoarthritis; cGAS-STING pathway; mtDNA; Pyroptosis; Innate immunity

摘要：OA is no longer regarded as a purely "wear and tear" disease, but rather a multifactorial, low-grade inflammatory disease in which the innate immune pathway coordinates cartilage degeneration, synovitis, and abnormal subchondral bone remodeling. This article re-examines the pathogenesis of OA through the cGAS-STING pathway and its intersection with mitochondrial damage and pyroptosis. We summarized the evidence of mitochondrial dysfunction and mtDNA cytoplasmic escape induced by pathways such as mechanical overload, oxidative stress, and mitochondrial autophagy disorder. The leaked mtDNA activates the cGAS-STING pathway, thereby increasing the production of IFN-I and inflammatory cytokines. Meanwhile, mtDNA and reactive oxygen species provide initiation and activation signals for NLRP3 and AIM2 inflammasome, eventually leading to pyroptosis of cells. We propose a "multilevel coupling" hypothesis in which mtDNA leakage, cGAS-STING activation, and pyroptosis act as mutually reinforcing nodes that sustain sterile inflammation and accelerate OA progression, highlighting this axis as a promising target for disease-modifying therapy. The Translational Potential of this Article:This review outlines the mitochondrial damage-cGAS-STINGpyroptosis axis as a potential driver of OA, highlighting its role in sustaining chronic joint inflammation. By identifying key points for intervention: mitochondrial protection, cGAS-STING modulation, and inflammasome inhibition, this framework supports the development of targeted or combination therapies, offering a path toward disease-modifying treatments for OA.