{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T23:29:25Z","timestamp":1783380565570,"version":"3.54.6"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1997,3,1]],"date-time":"1997-03-01T00:00:00Z","timestamp":857174400000},"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":[[1997,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The mechanisms involved in normal cranial suture development and fusion as well as the pathophysiology of craniosynostosis, a premature fusion of the cranial sutures, are not well understood. Transforming growth factor-\u03b2 isoforms (TGF-\u03b21, \u03b22, and \u03b23) are abundant in bone and stimulate calvarial bone formation when injected locally in vivo. To gain insight into the role of these factors in normal growth and development of cranial sutures and the possible etiology of premature cranial suture fusion, we examined the temporal and spatial expression of TGF-\u03b2 isoforms during normal cranial suture development in the rat. In the Sprague-Dawley rat, only the posterior frontal cranial suture undergoes fusion between 12 and 22 days of age, while all other cranial sutures remain patent. Therefore, immunohistochemical analysis of the fusing posterior frontal suture was compared with the patent sagittal suture at multiple time points from the fetus through adult. Whereas the intensity of immunostaining was the same in the posterior frontal and sagittal sutures in the fetal rat, there was increased immunoreactivity for TGF-\u03b2 isoforms in the actively fusing posterior frontal suture compared with the patent sagittal suture starting 2 days after birth and continuing until approximately 20 days. There were intensely immunoreactive osteoblasts present during fusion of the posterior frontal suture. In contrast, the patent sagittal suture was only slightly immunoreactive. A differential immunostaining pattern was observed among the TGF-\u03b2 isoforms; TGF-\u03b22 was the most immunoreactive isoform and was also most strongly associated with osteoblasts adjacent to the dura and the margin of the fusing suture. Since the increased expression of TGF-\u03b22 during suture fusion suggested a possible regulatory role, recombinant TGF-\u03b22 was added directly to the posterior frontal and sagittal sutures in vivo to determine if suture fusion could be initiated. Exogenously added TGF-\u03b22 stimulated fusion of the ectocranial surface of the posterior frontal suture. These data provide evidence for a regulatory role for these growth factors in cranial suture development and fusion. Additionally, the intense immunostaining for TGF-\u03b22 in the dura mater underlying the fusing suture supports a role for the dura mater in suture fusion. It is possible that premature or excessive expression of these factors may be involved in the etiopathogenesis of craniosynostosis and that modulation of the growth factor profile at the suture site may have potential therapeutic value.<\/jats:p>","DOI":"10.1359\/jbmr.1997.12.3.311","type":"journal-article","created":{"date-parts":[[2006,6,9]],"date-time":"2006-06-09T02:31:59Z","timestamp":1149820319000},"page":"311-321","source":"Crossref","is-referenced-by-count":115,"title":["Studies in Cranial Suture Biology: Part I. Increased Immunoreactivity for TGF-\u03b2 Isoforms (\u03b21, \u03b22, and \u03b23) During Rat Cranial Suture Fusion"],"prefix":"10.1093","volume":"12","author":[{"given":"Douglas A.","family":"Roth","sequence":"first","affiliation":[{"name":"The Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, New York, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Longaker","sequence":"additional","affiliation":[{"name":"The Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, New York, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph G.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"The Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, New York, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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