{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T20:08:31Z","timestamp":1782331711239,"version":"3.54.5"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24390444"],"award-info":[{"award-number":["24390444"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26462972"],"award-info":[{"award-number":["26462972"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J Oral Sciences"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>To accomplish effective periodontal regeneration for periodontal defects, several regenerative methods using growth and differentiation factors, including bone morphogenetic proteins (<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>s), have been developed. Bone morphogenetic protein\u20109 exhibits the most potent osteogenic activity of this growth factor family. However, it is unclear whether exogenous <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109 can induce osteogenic differentiation in human periodontal ligament (<jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content>) fibroblasts. Here, we examined the effects of recombinant human (rh) <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109 on osteoblastic differentiation in human <jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content> fibroblasts in vitro, compared with rh<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20102. Recombinant human <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109 potently induced alkaline phosphatase (<jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content>) activity, mineralization, and increased expression of runt\u2010related transcription factor\u2010<jats:italic>2<\/jats:italic>\/core binding factor alpha <jats:italic>1 (RUNX2\/CBFA1)<\/jats:italic>, osterix, inhibitor of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> binding\/differentiation\u20101 (<jats:italic><jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>1<\/jats:italic>), osteopontin, and bone sialoprotein genes, compared with rh<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20102. The levels of rh<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109\u2010induced osterix and <jats:italic>ALP <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> were significantly reduced in activin receptor\u2010like kinase\u20101 and \u20102 small interfering <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>)\u2010transfected human <jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content> fibroblasts. Recombinant human <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109\u2010induced <jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content> activity was not inhibited by noggin, in contrast to rh<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20102 induced <jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content> activity, which was. Phosphorylation of <jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content>1\/5\/8 in human <jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content> fibroblasts was induced by addition of rh<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109. Recombinant human <jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109\u2010induced <jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content> activity was suppressed by <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>203580, <jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>600125, and U0126, which are inhibitors of p38, c\u2010Jun N\u2010terminal kinase (<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>), and extracellular signal\u2010regulated kinase 1\/2 (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2), respectively. Our data suggest that rh<jats:styled-content style=\"fixed-case\">BMP<\/jats:styled-content>\u20109 is a potent inducer of the differentiation of human <jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content> fibroblasts into osteoblast\u2010like cells and that this may be mediated by the <jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content> and mitogen\u2010activated protein kinase (p38, <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2, and <jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>) pathways.<\/jats:p>","DOI":"10.1111\/eos.12249","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T13:02:18Z","timestamp":1455627738000},"page":"151-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Recombinant human bone morphogenetic protein\u20109 potently induces osteogenic differentiation of human periodontal ligament fibroblasts"],"prefix":"10.1111","volume":"124","author":[{"given":"Sawako","family":"Fuchigami","sequence":"first","affiliation":[{"name":"Department of Periodontology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Periodontology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirara","family":"Furue","sequence":"additional","affiliation":[{"name":"Department of Periodontology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Sena","sequence":"additional","affiliation":[{"name":"Department of Periodontology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiya","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Department of Periodontology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Periodontology Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"},{"name":"Research and Education Center for Advanced Oral Sciences Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima 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