{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:16:17Z","timestamp":1784024177464,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteoarthritis (OA) is one of the most prevalent joint diseases in aged people and characterized by articular cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Recent advances in OA research have clearly shown that OA development is associated with aberrant DNA methylation status of many OA\u2010related genes. As one of most important cartilage degrading proteases in OA, a disintegrin and metalloproteinase with thrombospondin motifs subtype 5 (ADAMTS\u20105) is activated to mediate cartilage degradation in human OA and experimental murine OA models. The pathological factors and signaling pathways mediating ADAMTS\u20105 activation during OA development are not well defined and have been a focus of intense research. ADAMTS\u20105 promoter is featured by CpG islands. So far there have been no reports concerning the DNA methylation status in ADAMTS\u20105 promoter during OA development. In this study, we sought to investigate DNA methylation status in ADAMTS\u20105 promoter, the role of DNA methylation in ADAMTS\u20105 activation in OA, and the underlying mechanisms. The potential for anti\u2010OA intervention therapy which is based on modulating DNA methylation is also explored. Our results showed that DNA methyltransferases 1 (Dnmt1) downregulation\u2010associated ADAMTS\u20105 promoter demethylation played an important role in ADAMTS\u20105 activation in OA, which facilitated SPI\u20101 binding on ADAMTS\u20105 promoter to activate ADAMTS\u20105 expression. More importantly, OA pathological phenotype of mice was alleviated in response to Dnmt1\u2010induced DNA methylation of ADAMTS\u20105 promoter. Our study will benefit not only for deeper insights into the functional role and regulation mechanisms of ADAMTS\u20105 in OA, but also for the discovery of disease\u2010modifying OA drugs\u00a0on the basis of ADAMTS\u20105 via modulating DNA methylation status.<\/jats:p>","DOI":"10.1002\/jcp.31170","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T12:39:29Z","timestamp":1703680769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["DNA demethylation of promoter region orchestrates SPI\u20101\u2010induced ADAMTS\u20105 expression in articular cartilage of osteoarthritis mice"],"prefix":"10.1002","volume":"239","author":[{"given":"Zhixin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Qilu Hospital of Shandong University Jinan 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