{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:04:33Z","timestamp":1793876673404,"version":"4.7.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073494"],"award-info":[{"award-number":["82073494"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773372"],"award-info":[{"award-number":["81773372"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Kashin-Beck disease (KBD) is a nutrition-related osteoarthropathy characterized by excessive apoptosis and matrix destruction. Micronutrient selenium (Se) deficiency is recognized as a major environmental risk factor. This study aimed to investigate the role of RUNX2 in cartilage injury associated with KBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      RUNX2 expression in articular cartilage from KBD patients was assessed by immunohistochemistry.\n                      <jats:italic>RUNX2<\/jats:italic>\n                      mRNA expression and promoter methylation were analyzed using qRT-PCR and qMSP. A chondrocyte injury model was established under Se-deficient conditions, while a\n                      <jats:italic>RUNX2<\/jats:italic>\n                      overexpression model was generated by lentiviral transfection and further analyzed by RNA sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The proportion of RUNX2-positive cells in KBD cartilage was significantly higher than in controls.\n                      <jats:italic>RUNX2<\/jats:italic>\n                      mRNA levels were elevated, whereas methylation levels were reduced in KBD samples. Inhibition of DNA methylation confirmed that decreased methylation of\n                      <jats:italic>RUNX2<\/jats:italic>\n                      promoted its transcription. In Se-deficient chondrocytes, decreased\n                      <jats:italic>RUNX2<\/jats:italic>\n                      methylation, increased RUNX2 expression, and higher rates of apoptosis and necrosis were observed, all of which were reversed by Se supplementation. Moreover, RUNX2 overexpression further increased chondrocyte apoptosis and necrosis. Transcriptomic analysis revealed 263 upregulated and 216 downregulated genes, predominantly enriched in the TNF and MAPK signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Micronutrient Se deficiency may contribute to the pathogenesis of KBD by modulating RUNX2 expression and inducing excessive chondrocyte apoptosis, while Se supplementation exerts a protective effect. RUNX2 plays a critical role in KBD progression and may represent a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2025.1687954","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T06:29:06Z","timestamp":1764916146000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of selenium-mediated RUNX2 overexpression and its transcriptome alterations on Chondrocyte injury in Kashin Beck disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Di","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmin","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiquan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. 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