{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:44:12Z","timestamp":1785512652197,"version":"3.56.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background and aims:<\/jats:bold> Kashin-Beck disease (KBD) is a unique endemic osteochondropathy with unclear pathogenesis in China. T-2 toxin exposure has been identified as a significant risk factor of KBD. However, the mechanism of articular cartilage damage induced by T-2 toxin is a conundrum. We explored the role of the extracellular matrix-related gene TSG-6 in the articular chondrocyte damage process under the exposure of HT-2 toxin.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> TSG-6 was identified as a candidate gene by mining our previous gene expression profiling of KBD and verified by qRT-PCR and immunohistochemistry. Then, TSG-6 was silenced by RNA interference technology and overexpressed induction by TNF-\u03b1. Gradient concentrations of HT-2 toxin were added to intervene with C28\/I2 chondrocytes. MTT was used to observe the proliferation and cell viability of chondrocytes, and qRT-PCR was utilized to detect the expression changes of MMP1, MMP3, MMP13, COL2A1, and proteoglycan before and after treatments for verification.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> TSG-6 was upregulated in KBD chondrocytes at the mRNA level and upregulated in the superficial, middle, and deep zones of KBD cartilage. After TSG-6 silencing, the expression of MMP1, MMP3, MMP13, and proteoglycan was significantly decreased while COL2A1 expression was significantly increased, which was reversed after the overexpression of TSG-6 induced by TNF-\u03b1 (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). The survival rate of chondrocytes was correspondingly reduced with an increase in the HT-2 toxin concentration. Compared with the blank control group, the expression of MMPs was increased in the intervention group of HT-2 toxin, while the expression of proteoglycan and COL2A1 decreased (<jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The upregulation of the TSG-6 gene may play a role in promoting the damage and degradation of the extracellular matrix in KBD chondrocytes under the exposure of HT-2 toxin.<\/jats:p>","DOI":"10.3389\/fgene.2022.1064565","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T05:03:02Z","timestamp":1668747782000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Abnormal expression of TSG-6 disturbs extracellular matrix homeostasis in chondrocytes from endemic osteoarthritis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yujie","family":"Ning","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feihong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaowei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmou","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"924.2","DOI":"10.1136\/annrheumdis-2015-eular.4767","article-title":"AB0101\u2005Viral expression of TSG-6 can stimulate osteophyte formation in experimental osteoarthritis","volume":"74","author":"Broeren","year":"2015","journal-title":"Ann. 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