{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:18:08Z","timestamp":1781191088838,"version":"3.54.1"},"reference-count":33,"publisher":"SAGE Publications","issue":"13-14","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>\n                    The five flat bones of developing cranial plates are bounded by fibrous sutures, which remain open during development to accommodate for the growing brain. Kdm6A is a demethylase that removes the epigenetic repressive mark, trimethylated lysine 27 on histone 3 (H3K27me3), from the promoters of osteogenic genes, and has previously been reported to promote osteogenesis in cranial bone cells. This study generated a mesenchyme-specific deletion of a histone demethylase,\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    , to assess the effects of\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    loss, in cranial plate development and suture fusion. The results showed that the loss of\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    in\n                    <jats:italic toggle=\"yes\">\n                      Prx1\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    cranial cells caused increased anterior width and length in the calvaria of both male and female mice. However, the posterior length was further decreased in female mice. Moreover, loss of\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    resulted in suppression of late suture development and calvarial frontal bone formation predominantly in female mice. In vitro assessment of calvaria cultures isolated from female\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    knockout mice found significantly suppressed calvarial osteogenic differentiation potential, associated with decreased gene expression levels of\n                    <jats:italic toggle=\"yes\">Runx2<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Alkaline Phosphatase<\/jats:italic>\n                    and increased levels of the suppressive mark, H3K27me3, on the respective gene promoters. Conversely, cultured calvaria bone cultures isolated from male\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    knockout mice exhibited an increased osteogenic differentiation potential. Interestingly, the milder effects on cranial suture development in\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    knockout male mice, were associated with an overcompensation of the\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    Y-homolog,\n                    <jats:italic toggle=\"yes\">Kdm6c<\/jats:italic>\n                    , and increased expression levels of\n                    <jats:italic toggle=\"yes\">Kdm6b<\/jats:italic>\n                    in calvarial bone cultures. Taken together, these data demonstrate a role for\n                    <jats:italic toggle=\"yes\">Kdm6a<\/jats:italic>\n                    during calvarial development and patterning, predominantly in female mice, and highlight the potential role of Kdm6 family members in patients with unexplained craniofacial deformities.\n                  <\/jats:p>","DOI":"10.1089\/scd.2023.0022","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T03:06:26Z","timestamp":1681959986000},"page":"398-409","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["KDM6A-Mediated Regulation of Cranial Frontal Bone Suture Fusion in Mice Is Sex Dependent"],"prefix":"10.1177","volume":"32","author":[{"given":"Clara","family":"Pribadi","sequence":"first","affiliation":[{"name":"Mesenchymal Stem Cell Laboratory, School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia."},{"name":"Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Cakouros","sequence":"additional","affiliation":[{"name":"Mesenchymal Stem Cell Laboratory, School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia."},{"name":"Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Camp","sequence":"additional","affiliation":[{"name":"Mesenchymal Stem Cell Laboratory, School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia."},{"name":"Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Anderson","sequence":"additional","affiliation":[{"name":"Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia."},{"name":"Adelaide Craniofacial Unit, Women and Children Hospital, North Adelaide, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-3084","authenticated-orcid":false,"given":"Stan","family":"Gronthos","sequence":"additional","affiliation":[{"name":"Mesenchymal Stem Cell Laboratory, School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia."},{"name":"Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, 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