{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:34:22Z","timestamp":1792460062553,"version":"4.5.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T00:00:00Z","timestamp":1427414400000},"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":["J Dent Res"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>Cleidocranial dysplasia (CCD) is characterized by the runt-related transcription factor 2 (RUNX2) mutation, which results in delayed tooth eruption due to disturbed functions of dental follicle. Accumulating evidence has revealed a key regulatory circuit, including RUNX2, miR-31, and special AT-rich binding protein 2 (SATB2) acting in concert in mesenchymal stem cell homeostasis and functions. However, whether such a regulatory loop works in dental follicle cells (DFCs) remains unknown. Herein, we investigated the roles of RUNX2-miR-31-SATB2 in DFCs from patients with CCD (DFCs-CCD) to advance our understanding regarding physical tooth eruption. We identified a novel mutation on exon 5 (c.634T&gt;G, p.T212P) in RUNX2 via exome sequencing in the CCD patient with typical clinical presentations. Compared with DFCs from healthy donors, DFCs-CCD displayed significantly lower osteogenic, osteoclast-inductive, and matrix-degrading capacities and had lower RUNX2 (a transcriptional inhibitor of miR-31), higher miR-31, and downregulated SATB2. Lower ratios of RANKL\/OPG and RANKL\/RANK, as well as decreased expression of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 2 (MMP2), would lead to inactivation of osteoclasts and suppression of bone matrix remodeling in DFCs-CCD. Furthermore, the roles of the RUNX2-miR-31-SATB2 loop in DFCs-CCD were revealed by endogenous miR-31 knockdown, which resulted in increased SATB2 and RUNX2, as well as osteoclast-inductive and matrix degradation capacities. Conversely, SATB2, RUNX2, MMP9, MMP2, and osteoclast-inductive factors expression declined upon ectopic miR-31 overexpression in normal DFCs. Importantly, neonatal mice with in vivo siRUNX2 delivery exhibited less activated osteoclasts around dental follicles and delayed tooth eruption. Together, these results suggest that RUNX2 mutation\/haploinsufficiency disturbs osteoclast-inductive signaling in DFCs, which may be responsible for delayed tooth eruption in CCD patients. Manipulation of the RUNX2-miR-31-SATB2 loop may be a potential way to facilitate tooth eruption in CCD patients.<\/jats:p>","DOI":"10.1177\/0022034515578908","type":"journal-article","created":{"date-parts":[[2015,3,29]],"date-time":"2015-03-29T00:50:31Z","timestamp":1427590231000},"page":"936-944","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":53,"title":["Dental Follicle Cells Participate in Tooth Eruption via the RUNX2-MiR-31-SATB2 Loop"],"prefix":"10.1177","volume":"94","author":[{"given":"J.","family":"Ge","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Guo","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Fu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China"},{"name":"Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,3,27]]},"reference":[{"key":"bibr1-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.389"},{"key":"bibr2-0022034515578908","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.21.13674"},{"key":"bibr3-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30927"},{"key":"bibr4-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510369304"},{"key":"bibr5-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050503"},{"key":"bibr6-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24668"},{"key":"bibr7-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0686"},{"key":"bibr8-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.042"},{"key":"bibr9-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.05.012"},{"key":"bibr10-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24792"},{"key":"bibr11-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1111\/ocr.12000"},{"key":"bibr12-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302457200"},{"key":"bibr13-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01597.x"},{"key":"bibr14-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.05.024"},{"key":"bibr15-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509341629"},{"key":"bibr16-0022034515578908","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2008.41.4.322"},{"key":"bibr17-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084201"},{"key":"bibr18-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0127"},{"key":"bibr19-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(84)90105-5"},{"issue":"3","key":"bibr20-0022034515578908","first-page":"177","volume":"36","author":"Mundlos S","year":"1999","journal-title":"J Med Genet"},{"key":"bibr21-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80260-3"},{"issue":"3","key":"bibr22-0022034515578908","first-page":"311","volume":"72","author":"Okada Y","year":"1995","journal-title":"Lab Invest"},{"key":"bibr23-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-011-9356-0"},{"key":"bibr24-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10043"},{"key":"bibr25-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12113"},{"key":"bibr26-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.19.8581-8591.2005"},{"key":"bibr27-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.06.025"},{"key":"bibr28-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1177\/154405910208101004"},{"key":"bibr29-0022034515578908","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-6343.2009.01439.x"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0022034515578908","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0022034515578908","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0022034515578908","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:05:41Z","timestamp":1777496741000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0022034515578908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,27]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1177\/0022034515578908"],"URL":"https:\/\/doi.org\/10.1177\/0022034515578908","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,27]]}}}