{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T16:15:49Z","timestamp":1777133749950,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR070864"],"award-info":[{"award-number":["AR070864"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR077530"],"award-info":[{"award-number":["AR077530"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Adult skeletal stem cells (SSCs) that give rise to chondrocytes, osteocytes, and stromal cells as progeny have been shown to contribute to cartilage regeneration in osteoarthritis (OA). Understanding extrinsic and intrinsic regulators of SSC fate and function can therefore identify putative candidate factors to enhance cartilage regeneration. This study explores how the DNA hydroxymethylase Tet1 regulates SSC function in OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the differences in the SSC lineage tree and differentiation potential in neonatal and adult Tet1<jats:sup>+\/+<\/jats:sup> and Tet1<jats:sup>\u2212\/\u2212<\/jats:sup> mice with and without injury and upon OA induction and progression. Using RNA sequencing, the transcriptomic differences between SSCs and bone cartilage stroma progenitor cells (BCSPs) were identified in Tet1<jats:sup>+\/+<\/jats:sup> mice and Tet1<jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Loss of Tet1 skewed the SSC lineage tree by expanding the SSC pool and enhanced the chondrogenic potential of SSCs and BCSPs. Tet1 inhibition led to enhanced chondrogenesis in human SSCs and chondroprogenitors isolated from human cartilage. Importantly, TET1 inhibition in vivo in late stages of a mouse model of OA led to increased cartilage regeneration. Transcriptomic analyses of SSCs and BCSPs lacking Tet1 revealed pathway alterations in transforming growth factor \u03b2 signaling, melatonin degradation, and cartilage development\u2013associated genes. Lastly, we report that use of the hormone melatonin can dampen inflammation and improve cartilage health.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although Tet1 is a broad epigenetic regulator, melatonin can mimic the inhibition ability of TET1 to enhance the chondrogenic ability of SSCs. Melatonin administration has the potential to be an attractive stem cell\u2013based therapy for cartilage regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42678","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T09:20:38Z","timestamp":1692782438000},"page":"216-230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>TET1<\/scp> Regulates Skeletal Stem\u2013Cell Mediated Cartilage Regeneration"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8587-5890","authenticated-orcid":false,"given":"Akshay","family":"Pandey","sequence":"first","affiliation":[{"name":"Stanford University  Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malachia","family":"Hoover","sequence":"additional","affiliation":[{"name":"Stanford University  Stanford 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