{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:51:58Z","timestamp":1783338718838,"version":"3.54.6"},"reference-count":38,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T00:00:00Z","timestamp":1645833600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001001"],"award-info":[{"award-number":["82001001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Funding of West China Hospital of Stomatology","award":["RCDWJS2020-21"],"award-info":[{"award-number":["RCDWJS2020-21"]}]},{"name":"Research Funding of West China Hospital of Stomatology","award":["RD-02-202101"],"award-info":[{"award-number":["RD-02-202101"]}]},{"name":"Innovation Program of Chengdu City","award":["2019-YF05-01236-SN"],"award-info":[{"award-number":["2019-YF05-01236-SN"]}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE025866"],"award-info":[{"award-number":["R01DE025866"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["BX20190224"],"award-info":[{"award-number":["BX20190224"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR070877"],"award-info":[{"award-number":["R01AR070877"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postdoctoral Foundation of Sichuan University","award":["2020SCU12018"],"award-info":[{"award-number":["2020SCU12018"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>\n                    Calvaria development is distinct from limb formation. Craniosynostosis is a skull deformity characterized by premature cranial suture fusion due to the loss of the GNAS gene and, consequently, its encoded protein G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    . This birth defect requires surgery, with potential lethal consequences. So far, hardly any early-stage nonsurgical interventions for GNAS loss-related craniosynostosis are available. Here, we investigated the role of the Gnas gene in mice in guarding the distinctiveness of intramembranous ossification and how loss of Gnas triggered endochondral-like ossification within the cranial sutures. Single-cell RNA sequencing (scRNA-seq) of normal neonatal mice cranial suture chondrocytes showed a Hedgehog (Hh) inactivation pattern, which was associated with G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    signaling activation. Loss of Gnas evoked chondrocyte-to-osteoblast fate conversion and resulted in cartilage heterotopic ossification (HO) within cranial sutures and fontanels of the mouse model, leading to a skull deformity resembling craniosynostosis in patients with loss of GNAS. Activation of ectopic Hh signaling within cranial chondrocytes stimulated the conversion of cell identity through a hypertrophy-like stage, which shared features of endochondral ossification in vivo. Reduction of Gli transcription activity by crossing with a loss-of-function Gli2 allele or injecting GLI1\/2 antagonist hindered the progression of cartilage HO in neonatal stage mice. Our study uncovered the role of G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    in maintaining cranial chondrocyte identity during neonatal calvaria development in mice and how reduction of Hh signaling could be a nonsurgical intervention to reduce skull deformity in craniosynostosis due to loss of GNAS.\n                  <\/jats:p>","DOI":"10.1177\/00220345221075215","type":"journal-article","created":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T08:11:52Z","timestamp":1645863112000},"page":"931-941","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>Gnas<\/i>\n                    Loss Causes Chondrocyte Fate Conversion in Cranial Suture Formation"],"prefix":"10.1177","volume":"101","author":[{"given":"R.","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, Boston, MA, USA"},{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,2,26]]},"reference":[{"key":"bibr1-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.20.4753"},{"key":"bibr2-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24196"},{"key":"bibr3-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb2233"},{"key":"bibr4-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2018.11.019"},{"key":"bibr5-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02351"},{"key":"bibr6-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0457-8"},{"key":"bibr7-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1101\/gad.348151.120"},{"key":"bibr8-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1126\/science.aas8935"},{"key":"bibr9-00220345221075215","first-page":"1487","author":"Graul-Neumann LM","year":"2009","journal-title":"149A(7):"},{"key":"bibr10-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-020-00780-6"},{"key":"bibr11-00220345221075215","doi-asserted-by":"crossref","unstructured":"Holmbeck K, Bianco P, Chrysovergis K, Yamada S, Birkedal-Hansen H. 2003. MT1-MMP-dependent, apoptotic remodeling of unmineralized cartilage: a critical process in skeletal growth. J Cell Biol. 163(3):661\u2013671.","DOI":"10.1083\/jcb.200307061"},{"key":"bibr12-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107871"},{"key":"bibr13-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.018"},{"key":"bibr14-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115539"},{"key":"bibr15-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2019.12.004"},{"key":"bibr16-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714313114"},{"key":"bibr17-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.1739"},{"key":"bibr18-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10092"},{"key":"bibr19-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02546"},{"key":"bibr20-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1691-4"},{"key":"bibr21-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb4416"},{"key":"bibr22-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-019-04278-x"},{"key":"bibr23-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2252"},{"key":"bibr24-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24801-6"},{"key":"bibr25-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal2913"},{"key":"bibr26-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0989-6"},{"key":"bibr27-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3067"},{"key":"bibr28-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02480"},{"key":"bibr29-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011262"},{"key":"bibr30-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.12.004"},{"key":"bibr31-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20667"},{"key":"bibr32-00220345221075215","doi-asserted-by":"crossref","unstructured":"Tambuyzer E, Vandendriessche B, Austin CP, Brooks PJ, Larsson K, Miller Needleman KI, Valentine J, Davies K, Groft SC, Preti R, et al. 2020. Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nat Rev Drug Discov. 19(2):93\u2013111.","DOI":"10.1038\/s41573-019-0049-9"},{"key":"bibr33-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.03.019"},{"key":"bibr34-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9945-5"},{"key":"bibr35-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/nature01545"},{"key":"bibr36-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.08.025"},{"key":"bibr37-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0034-7"},{"key":"bibr38-00220345221075215","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.037"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345221075215","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345221075215","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345221075215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:09:46Z","timestamp":1777496986000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345221075215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,26]]},"references-count":38,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1177\/00220345221075215"],"URL":"https:\/\/doi.org\/10.1177\/00220345221075215","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,26]]}}}