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Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The obesity\u2010related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue\u2010derived EVs (Ad\u2010EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad\u2010EVs in obese state were identified by microRNA\u2010seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad\u2010EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad\u2010EVs secretion by knocking out the geranylgeranyl diphosphate synthase (<jats:italic>Ggpps<\/jats:italic>) gene in adipose tissue significantly inhibited the obesity\u2010induced aggravation of TMJ OA. MiR\u20103074\u20105p played an important role in this process .<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad\u2010EVs and the miR\u20103074\u20105p may represent a promising therapeutic strategy for obesity\u2010related TMJ OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>High\u2010fat\u2010diet\u2010induced obesity aggravate the progression of TMJ OA in mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of miR\u20103074\u20105p\/SMAD4 pathway in chondrocyte alleviated the effect of HFD\u2010EVs on TMJ OA.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70029","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T05:21:29Z","timestamp":1727760089000},"source":"Crossref","is-referenced-by-count":14,"title":["Adipose tissue\u2010derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity"],"prefix":"10.1002","volume":"14","author":[{"given":"Baochao","family":"Li","sequence":"first","affiliation":[{"name":"Nanjing Stomatological Hospital &amp; The State Key Laboratory of Pharmaceutical Biotechnology &amp; Jiangsu Key Laboratory of Molecular Medicine Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Jin","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital &amp; The State Key Laboratory of Pharmaceutical Biotechnology &amp; Jiangsu Key Laboratory of Molecular Medicine Medical School, Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Stomatological Hospital &amp; The State Key Laboratory of Pharmaceutical Biotechnology &amp; Jiangsu Key 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