{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:27:38Z","timestamp":1790836058228,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The growth plate is the primary site of longitudinal bone growth with chondrocytes playing a pivotal role in endochondral bone development. Chondrocytes undergo a series of differentiation steps, resulting in the formation of a unique hierarchical columnar structure comprising round, proliferating, pre\u2010hypertrophic, and hypertrophic chondrocytes. Pre\u2010hypertrophic chondrocytes, which exist in the transitional stage between proliferating and hypertrophic stages, are a critical cell population in the growth plate. However, the molecular basis of pre\u2010hypertrophic chondrocytes remains largely undefined. Here, we employed scRNA\u2010seq analysis on fluorescently labeled growth plate chondrocytes for their molecular characterization. Serine incorporator 5 (<jats:italic>Serinc5<\/jats:italic>) was identified as a marker gene for pre\u2010hypertrophic chondrocytes. Histological analysis revealed that Serinc5 is specifically expressed in pre\u2010hypertrophic chondrocytes, overlapping with Indian hedgehog (Ihh). Serinc5 represses cell proliferation and <jats:italic>Col2a1<\/jats:italic> and <jats:italic>Acan<\/jats:italic> expression by inhibiting the transcriptional activity of Sox9 in primary chondrocytes. Chromatin profiling using ChIP\u2010seq and ATAC\u2010seq revealed an active enhancer of <jats:italic>Serinc5<\/jats:italic> located in intron 1, with its chromatin status progressively activated during chondrocyte differentiation. Collectively, our findings suggest that Serinc5 regulates sequential chondrocyte differentiation from proliferation to hypertrophy by inhibiting Sox9 function in pre\u2010hypertrophic chondrocytes, providing novel insights into the mechanisms underlying chondrocyte differentiation in growth plates.<\/jats:p>","DOI":"10.1002\/jcp.31490","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T06:58:31Z","timestamp":1732172311000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre\u2010Hypertrophic Chondrocytes"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4367-9343","authenticated-orcid":false,"given":"Kenji","family":"Hata","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry Osaka University Graduate School of 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