{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:45:14Z","timestamp":1792147514672,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101006"],"award-info":[{"award-number":["82101006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cementum shares similar characteristics with bone in terms of biochemical composition. Recent studies have reported that glycolysis is the main energy source driving osteoblast differentiation, but the role of glycolysis in cementoblast differentiation remains elusive. Previously, we found Sirtuin 6 (SIRT6) suppressed cementoblast differentiation and mineralization via inhibiting glucose transporter 1 (GLUT1), indicating that glycolysis may also be required for cementogenesis. However, the underlying mechanisms remain largely unknown. In this study, we observed that the expression of glycolytic enzymes increased progressively during cementoblast differentiation. Measurements of extracellular acidification rate, glucose uptake, lactate release, and gain\u2010and\u2010loss of function demonstrated that overexpressing SIRT6 in immortalized mouse cementoblasts (OCCM\u201030) suppressed cementoblast glycolysis. Mechanistically, chromatin immunoprecipitation assay results revealed that SIRT6 inhibits insulin receptor substrate 2 (IRS2) transcription by deacetylating histone H3 at lysine K9 (H3K9). Overexpression of IRS2 promoted OCCM\u201030 glycolysis and mineralization through phosphoinositide 3\u2010kinase (PI3K)\/protein kinase B (AKT) signaling pathway, whereas SIRT6 significantly inhibited PI3K\/AKT pathway activity. Overall, our results demonstrate that SIRT6 inhibits IRS2 transcription by deacetylating histone H3K9, thereby reducing PI3K\/AKT signaling\u2010induced glycolysis and suppressing cementoblast mineralization.<\/jats:p>","DOI":"10.1002\/cbin.70226","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:53:08Z","timestamp":1792057988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SIRT6 Inhibits Glycolysis and Cementogenesis via Targeting IRS2"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9544-9285","authenticated-orcid":false,"given":"Liyuan","family":"Huang","sequence":"first","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral Biomedical Hangzhou Zhejiang P.R. 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