{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T06:00:40Z","timestamp":1785477640690,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"High Education Joint Research Project of Shanxi Province","award":["2020GXLH-Y-014"],"award-info":[{"award-number":["2020GXLH-Y-014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Previous studies revealed that low expression of Selenoprotein S (SELS) could enhance osteogenic differentiation, but the underlying mechanisms remain unclear. In this study, we aimed to elucidate the role of SELS and its transcription-factor-based regulatory mechanism during osteogenic differentiation. In comparison with 12-week-old mice, which represent the stage of stable osteogenic differentiation, 3-week-old mice, representing the active ossification stage, showed significantly higher levels of SELS in the mandible. Transcriptomic analysis revealed that SELS is primarily associated with extracellular matrix organization and collagen biosynthesis during mandibular development. In bone marrow mesenchymal stem cells (BMSCs) with SELS knockdown, SP7 levels were elevated after 7 days of osteogenic induction in vitro. Consistently, immunohistochemical and immunofluorescence staining confirmed increased SP7 expression in the mandibles of 7-week-old Sels knockout mice. Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) analysis demonstrated that SP7 directly binds to the heat shock protein 47 (HSP47) promoter and negatively regulates its transcription. Consequently, upregulation of SP7 following SELS knockdown led to downregulation of HSP47 and concurrent upregulation of the SP7 downstream targets, collagen type I alpha 1 chain (COL1A1) and Secreted protein acidic and rich in cysteine (SPARC). SELS expression is upregulated during active osteogenesis. Low expression of SELS regulates osteogenic differentiation in a bidirectional and fine-tuned manner through the SP7\u2013HSP47\/COL1A1\/SPARC axis.<\/jats:p>","DOI":"10.3390\/cimb47090677","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:09:53Z","timestamp":1756080593000},"page":"677","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low Expression of Selenoprotein S Modulates Osteogenic Differentiation Through Bidirectional Regulation of the SP7\u2013HSP47\/COL1A1\/SPARC Axis"],"prefix":"10.3390","volume":"47","author":[{"given":"Hao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Shan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Shen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Yi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Qiu-Yue","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8593-3923","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Stomatology, First Affiliated Hospital, College of Medicine, Xi\u2019an Jiaotong University, 277 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bubenik, J.L., Miniard, A.C., and Driscoll, D.M. 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