{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:12:23Z","timestamp":1789456343521,"version":"build-2803163510"},"reference-count":63,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterotopic ossification (HO) is the aberrant formation of mature, lamellar bone in nonosseous tissue. Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disorder that causes progressive HO in the ligaments, tendons, and muscles throughout the body. FOP is attributed to an autosomal mutation in activin receptor-like kinase 2 (ALK2), a bone morphogenetic protein (BMP) type I receptor. Initial studies show that mutant ALK2 drives HO by constitutively activating the BMP signaling pathway. Recently, mutant ALK2 has been shown to transduce Smad1\/5 signaling and enhance chondrogenesis, calcification in response to Activin A, which normally signals through Smad2\/3 and inhibits BMP signaling pathway. Furthermore, Activin A induces heterotopic bone formation via mutant ALK2, while inhibition of Activin A blocks spontaneous and trauma-induced HO. In this manuscript, we describe the molecular mechanism of the causative gene ALK2 in FOP, mainly focusing on the prominent role of Activin A in HO. It reveals a potential strategy for prevention and treatment of FOP by inhibition of Activin A. Further studies are needed to explore the cellular and molecular mechanisms of Activin A in FOP in more detail.<\/jats:p>","DOI":"10.1042\/bsr20190377","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T15:45:14Z","timestamp":1563983114000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The role of Activin A in fibrodysplasia ossificans progressiva: a prominent mediator"],"prefix":"10.1042","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0343-1757","authenticated-orcid":false,"given":"Hui","family":"Lin","sequence":"first","affiliation":[{"name":"Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology and Department of Pathophysiology, School of Basic Medicine Sciences, Nanchang University Medical College, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuli","family":"Shi","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology and Department of Pathophysiology, School of Basic Medicine Sciences, Nanchang University Medical College, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Gao","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology and Department of Pathophysiology, School of Basic Medicine Sciences, Nanchang University Medical College, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Hua","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology and Department of Pathophysiology, School of Basic Medicine Sciences, Nanchang University Medical College, Nanchang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,8,2]]},"reference":[{"key":"2021111619453524100_B1","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.cytogfr.2015.12.007","article-title":"Common mutations in ALK2\/ACVR1, a multi-faceted receptor, have roles in distinct pediatric musculoskeletal and neural orphan disorders","volume":"27","author":"Pacifici","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"2021111619453524100_B2","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1080\/21678707.2017.1304211","article-title":"Hard targets for a second skeleton: therapeutic horizons for fibrodysplasia ossificans progressiva (FOP)","volume":"5","author":"Kaplan","year":"2017","journal-title":"Expert Opin. 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