{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T02:35:26Z","timestamp":1792377326553,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Osteoarthritis (OA) is one of the most common degenerative joint diseases and is associated with autophagy suppression. However, the molecular mechanism of autophagy regulation in the context of OA is not fully understood. In this study, we sought to determine the role that HECTD1 plays in the pathogenesis of OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used RNA sequencing analysis to explore the differential expression of E3 ubiquitin ligase genes in healthy human cartilage and human cartilage affected by OA. Using surgery\u2010 and aging\u2010induced OA mouse models, we comprehensively analyzed the function of the screened gene <jats:italic>Hectd1<\/jats:italic> in the development of OA; furthermore, we dissected the mechanism by which HECTD1 regulates autophagy and OA progression using a combination of molecular biologic, cell biologic, and biochemical approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HECTD1 was significantly down\u2010regulated in human OA cartilage samples compared to healthy cartilage samples. Overexpression of HECTD1 in mouse joints alleviated OA pathogenesis, whereas conditional depletion of <jats:italic>Hectd1<\/jats:italic> in cartilage samples aggravated surgery\u2010 and aging\u2010induced OA pathogenesis. Mechanistically, HECTD1 bound to Rubicon and ubiquitinated Rubicon at lysine residue 534, which targets Rubicon for proteasomal degradation. More importantly, HECTD1\u2010mediated Rubicon degradation regulated chondrocyte autophagy, leading to mitigation of stress\u2010induced chondrocyte death and the subsequent progression of OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HECTD1 plays a crucial role in the pathogenesis of OA, in that HECTD1 regulates chondrocyte autophagy by ubiquitinating and targeting Rubicon for proteasomal degradation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42369","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T14:38:37Z","timestamp":1663598317000},"page":"387-400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["HECTD1\u2010Mediated Ubiquitination and Degradation of Rubicon Regulates Autophagy and Osteoarthritis Pathogenesis"],"prefix":"10.1002","volume":"75","author":[{"given":"Shiyao","family":"Liao","sequence":"first","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University, Zhejiang, China, and Department of Orthopedic Surgery Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Shen","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University, Zhejiang China, and Department of Orthopedic Surgery The First Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral Implantology and Prosthodontics The Affiliated Stomatology Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-2536","authenticated-orcid":false,"given":"Hongwei","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyou","family":"Pan","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; 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