{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:07:35Z","timestamp":1710374855001},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T00:00:00Z","timestamp":1376611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Craniosynostosis, the premature fusion of one or more sutures between the calvarial bones, is a common birth defect. Mutations in genes encoding receptors for the transforming growth factor-beta (TGF\u03b2) family of signaling molecules have been associated with craniosynostosis, but how TGF\u03b2 signaling is regulated during suture development is not known. In the present study, we found that expression of Smad2 and Smad3, intracellular mediators of canonical TGF\u03b2 signaling, gradually increases during early postnatal suture development in rat in both the coronal suture (CS), which remains patent throughout life, and the posterior frontal suture (PFS), which undergoes programmed closure by postnatal day 22. The amounts of phosphorylated Smad2 and Smad3 proteins showed a similar gradual increase in the PFS and CS, but in the CS, Smad2\/3 activation was suppressed after neonatal day 10. The suppression of Smad2\/3 activation in the CS correlated with upregulation of Smad7 expression. We demonstrate that siRNA-mediated knockdown of Smad7 caused increased phosphorylation of Smad2 and Smad3 and induced osseous obliteration of the CS from postnatal days 10 to 22. The Smad7 siRNA-induced CS closure was associated with significantly increased levels of Fgf10 and phosphorylated ERK1\/2 in the suture mesenchyme. Moreover, addition of the Erk1\/2 inhibitor U0126 partially blocked Smad7-siRNA\u2013induced CS closure. These findings suggest that canonical TGF\u03b2 signaling induces suture closure at least in part through activation of FGF and ERK signaling and that Smad7 plays an important role in maintaining suture patency by suppressing canonical TGF\u03b2 signaling during suture development. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2066","type":"journal-article","created":{"date-parts":[[2013,8,19]],"date-time":"2013-08-19T14:24:47Z","timestamp":1376922287000},"page":"716-724","source":"Crossref","is-referenced-by-count":6,"title":["Smad7 Modulates TGF\u03b2 Signaling During Cranial Suture Development to Maintain Suture Patency"],"prefix":"10.1093","volume":"29","author":[{"given":"Hao","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Sichuan Provincial People's HospitalSichuan Provincial Academy of Medical ScienceChengduChina"},{"name":"State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of StomatologySichuan UniversityChengduChina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujuan","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of StomatologySichuan UniversityChengduChina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Lan","sequence":"additional","affiliation":[{"name":"Divsion of Plastic SurgeryCincinnati Children's Hospital Medical CenterCincinnatiOHUSA"},{"name":"Division of Developmental BiologyCincinnati Children's Hospital Medical CenterCincinnatiOHUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Sichuan Provincial People's HospitalSichuan Provincial Academy of Medical ScienceChengduChina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rulang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Divsion of Plastic SurgeryCincinnati Children's Hospital Medical CenterCincinnatiOHUSA"},{"name":"Division of Developmental BiologyCincinnati Children's Hospital Medical CenterCincinnatiOHUSA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, West China Hospital of StomatologySichuan UniversityChengduChina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,8,16]]},"reference":[{"issue":"2","key":"2024020318563441600_jbmr2066-bib-0001","first-page":"80","article-title":"Patterns of growth of the skull as revealed by vital staining","volume":"26","author":"Baer","year":"1954","journal-title":"Hum 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rat","volume":"102","author":"Moss","year":"1958","journal-title":"Am J Anat."},{"issue":"4","key":"2024020318563441600_jbmr2066-bib-0008","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/00006534-199604000-00001","article-title":"Studies in cranial suture biology: part II. Role of the dura in cranial suture fusion","volume":"97","author":"Roth","year":"1996","journal-title":"Plast Reconstr Surg."},{"issue":"6","key":"2024020318563441600_jbmr2066-bib-0009","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1097\/00006534-199805000-00002","article-title":"Studies in cranial suture biology: regional dura mater determines overlying suture biology","volume":"101","author":"Levine","year":"1998","journal-title":"Plast Reconstr Surg."},{"issue":"4","key":"2024020318563441600_jbmr2066-bib-0010","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/aja.1001980408","article-title":"Tissue interactions with underlying dura mater inhibit osseus obliteration of developing cranial sutures developmental dynamics","volume":"198","author":"Opperman","year":"1993","journal-title":"Dev Dyn."},{"issue":"12","key":"2024020318563441600_jbmr2066-bib-0011","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1002\/jbmr.5650101218","article-title":"Cranial sutures require tissue interactions with dura mater to resist osseous obliteration in vitro","volume":"10","author":"Opperman","year":"1995","journal-title":"J Bone Miner Res."},{"issue":"10","key":"2024020318563441600_jbmr2066-bib-0012","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/BF02724047","article-title":"Dura mater secretes soluble heparin-binding factors required for cranial suture morphogenesis","volume":"32","author":"Opperman","year":"1996","journal-title":"J In Vitro Cell Dev Biol Anim."},{"issue":"3","key":"2024020318563441600_jbmr2066-bib-0013","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1359\/jbmr.1997.12.3.311","article-title":"Studies in cranial suture biology: part I. 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