{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:04:26Z","timestamp":1777658666767,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,11,11]],"date-time":"2018-11-11T00:00:00Z","timestamp":1541894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fibrodysplasia ossificans progressiva (FOP) is a genetic disease characterized by heterotopic ossification (HO). The disease is caused by a mutation in the activin receptor type 1 (<jats:italic>ACVR1<\/jats:italic>) gene that enhances this receptor's responsiveness to Activin\u2010A. Binding of Activin\u2010A to the mutated ACVR1 receptor induces osteogenic differentiation. Whether Activin\u2010A also affects osteoclast formation in FOP is not known. Therefore we investigated its effect on the osteoclastogenesis\u2010inducing potential of periodontal ligament fibroblasts (PLF) from teeth of healthy controls and patients with FOP. We used western blot analysis of phosphorylated SMAD3 (pSMAD3) and quantitative polymerase chain reaction to assess the effect of Activin\u2010A on the PLF. PLF\u2010induced osteoclast formation and gene expression were studied by coculturing control and FOP PLF with CD14\u2010positive osteoclast precursor cells from healthy donors. Osteoclast formation was also assessed in control CD14 cultures stimulated by macrophage colony\u2010stimulating factor (M\u2010CSF) and receptor activator of nuclear factor kappa\u2010B ligand (RANK\u2010L). Although Activin\u2010A increased activation of the pSMAD3 pathway in both control and FOP PLF, it increased ACVR1, FK binding protein 12 (FKBP12), an inhibitor of DNA binding 1 protein (ID\u20101) expression only in FOP PLF. Activin\u2010A inhibited PLF mediated osteoclast formation albeit only significantly when induced by FOP PLF. In these cocultures, it reduced M\u2010CSF and dendritic cell\u2010specific transmembrane protein (DC\u2010STAMP) expression. Activin\u2010A also inhibited osteoclast formation in M\u2010CSF and RANK\u2010L mediated monocultures of CD14+ cells by inhibiting their proliferation.<\/jats:p><jats:p>This study brings new insight on the role of Activin A in osteoclast formation, which may further add to understanding FOP pathophysiology; in addition to the known Activin\u2010A\u2010mediated HO, this study shows that Activin\u2010A may also inhibit osteoclast formation, thereby further promoting HO formation.<\/jats:p>","DOI":"10.1002\/jcp.27693","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T06:10:07Z","timestamp":1542003007000},"page":"10238-10247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The effect of Activin\u2010A on periodontal ligament fibroblasts\u2010mediated osteoclast formation in healthy donors and in patients with fibrodysplasia ossificans progressiva"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-374X","authenticated-orcid":false,"given":"Ton","family":"Schoenmaker","sequence":"first","affiliation":[{"name":"Department of Periodontology Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenne","family":"Wouters","sequence":"additional","affiliation":[{"name":"Department of Periodontology Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra","family":"Micha","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics VU University Medical Center, Amsterdam Movement Sciences Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Forouzanfar","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Oral Pathology VU University Medical Center, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coen","family":"Netelenbos","sequence":"additional","affiliation":[{"name":"Internal Medicine, Endocrinology Section, VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. 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