{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:42:07Z","timestamp":1792158127802,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Developmental dysplasia of hip (DDH) is a hip joint disorder leading to subsequent osteoarthritis. Previous studies suggested collagen XI alpha 1 (COL11A1) as a potential gene in hip dysplasia and chondrocyte degeneration. However, no genetic association has reported COL11A1\u2010related cellular therapy as treatment of DDH and joint degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We report identified genetic association between COL11A1 locus and DDH with genome\u2010wide association study (GWAS). Further exome sequencing for familial DDH patients was conducted in different populations to identify potential pathogenic Col11A1 variants for familiar DDH. Further studies demonstrated involvement of COL11A1 expression was down\u2010regulated in femoral head cartilage of DDH patients and Col11a1\u2010KO mice with induced DDH. Col11a1\u2010KO mice demonstrated aggravated joint degeneration and severe OA phenotype. To explore the underlying mechanism of Col11a1 in cartilage and DDH development, we generated scRNA\u2010seq profiles for DDH and Col11a1\u2010KO cartilage, demonstrating disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1\u2013HIF1\u03b1\u2010mediated glycolysis\u2013OXPHOS shift in chondrocytes. Genetically and biologically inspired, we further fabricated an intra\u2010articular injection therapy to preventing cartilage degeneration by generating a Col11a1\u2010over\u2010expressed (OE) SMSC mini\u2010organoids. Col11a1\u2010OE organoids demonstrated superior chondrogenesis and ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up\u2010regulated Col11a1\/HIF1\u03b1\u2010mediated glycolysis in chondrocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We reported association between COL11A1 loci and DDH with GWAS and exome sequencing. Further studies demonstrated involvement of COL11A1 in DDH patients and Col11a1\u2010KO mice. ScRNA\u2010seq for DDH and Col11a1\u2010KO cartilage demonstrated disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1\u2013HIF1\u03b1\u2010mediated glycolysis\u2013OXPHOS shift in chondrocytes. Genetically and biologically inspired, an intra\u2010articular injection therapy was fabricated to prevent cartilage degeneration with Col11a1\u2010OE SMSC organoids. Col11a1\u2010OE organoids ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up\u2010regulated Col11a1\/HIF1\u03b1\u2010mediated glycolysis in chondrocytes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1574","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T08:26:13Z","timestamp":1707294373000},"source":"Crossref","is-referenced-by-count":19,"title":["Genetically inspired organoids prevent joint degeneration and alleviate chondrocyte senescence via Col11a1\u2013HIF1\u03b1\u2010mediated glycolysis\u2013OXPHOS metabolism shift"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3755-0853","authenticated-orcid":false,"given":"Ye","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Nanjing Medical University  Jiangsu China"},{"name":"Department of Orthopaedic Surgery Shanghai Key Laboratory of Orthopaedic Implants Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"You","sequence":"additional","affiliation":[{"name":"Department of Renal Diseases Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Shanghai Key Laboratory of Orthopaedic Implants Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Nanjing Medical University  Jiangsu 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