{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:24:16Z","timestamp":1791566656937,"version":"4.3.4"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100013117","name":"International Fibrodysplasia Ossificans Progressiva Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013117","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Center for Research in FOP and Related Disorders"},{"name":"Ian Cali Endowment for FOP Research"},{"DOI":"10.13039\/100013182","name":"Whitney Weldon Endowment for FOP Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013182","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cali-Weldon Professorship of FOP Research"},{"name":"NIH\/NIAMS","award":["R01-AR41916"],"award-info":[{"award-number":["R01-AR41916"]}]}],"content-domain":{"domain":["clinicalkey.jp","thebonejournal.com","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bone"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.bone.2017.10.027","type":"journal-article","created":{"date-parts":[[2017,10,31]],"date-time":"2017-10-31T19:45:51Z","timestamp":1509479151000},"page":"232-240","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":49,"special_numbering":"C","title":["Variable signaling activity by FOP ACVR1 mutations"],"prefix":"10.1016","volume":"109","author":[{"given":"Julia","family":"Haupt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M.","family":"Shore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.bone.2017.10.027_bb0005","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/ng1783","article-title":"A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva","volume":"38","author":"Shore","year":"2006","journal-title":"Nat. Genet."},{"issue":"3","key":"10.1016\/j.bone.2017.10.027_bb0010","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/humu.20868","article-title":"Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1","volume":"30","author":"Kaplan","year":"2009","journal-title":"Hum. Mutat."},{"issue":"303","key":"10.1016\/j.bone.2017.10.027_bb0015","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aac4358","article-title":"ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A","volume":"7","author":"Hatsell","year":"2015","journal-title":"Sci. Transl. Med."},{"issue":"7","key":"10.1016\/j.bone.2017.10.027_bb0020","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1359\/JBMR.050305","article-title":"Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA","volume":"20","author":"de la Pena","year":"2005","journal-title":"J. Bone Miner. Res."},{"issue":"3","key":"10.1016\/j.bone.2017.10.027_bb0025","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0046-8177(97)90133-7","article-title":"Bone morphogenetic protein 2\/4 in early fibromatous lesions of fibrodysplasia ossificans progressiva","volume":"28","author":"Gannon","year":"1997","journal-title":"Hum. Pathol."},{"key":"10.1016\/j.bone.2017.10.027_bb0030","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/00003086-199801000-00007","article-title":"Characterization of bone morphogenetic protein 4 receptor in fibrodysplasia ossificans progressiva","volume":"346","author":"Lanchoney","year":"1998","journal-title":"Clin. Orthop. Relat. Res."},{"key":"10.1016\/j.bone.2017.10.027_bb0035","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/00003086-200303000-00044","article-title":"Bone morphogenetic protein-4 regulation in fibrodysplasia ossificans progressiva","volume":"408","author":"Olmsted","year":"2003","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"8","key":"10.1016\/j.bone.2017.10.027_bb0040","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1056\/NEJM199608223350804","article-title":"Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva","volume":"335","author":"Shafritz","year":"1996","journal-title":"N. Engl. J. Med."},{"issue":"6659","key":"10.1016\/j.bone.2017.10.027_bb0045","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/37284","article-title":"TGF-beta signalling from cell membrane to nucleus through SMAD proteins","volume":"390","author":"Heldin","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.bone.2017.10.027_bb0050","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1146\/annurev.cellbio.21.022404.142018","article-title":"Specificity and versatility in tgf-beta signaling through Smads","volume":"21","author":"Feng","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."},{"issue":"10","key":"10.1016\/j.bone.2017.10.027_bb0055","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3810","article-title":"Targeting the TGFbeta signalling pathway in disease","volume":"11","author":"Akhurst","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"issue":"6958","key":"10.1016\/j.bone.2017.10.027_bb0060","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature02006","article-title":"Smad-dependent and Smad-independent pathways in TGF-beta family signalling","volume":"425","author":"Derynck","year":"2003","journal-title":"Nature"},{"issue":"44","key":"10.1016\/j.bone.2017.10.027_bb0065","doi-asserted-by":"crossref","first-page":"36990","DOI":"10.1074\/jbc.M112.365932","article-title":"Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva","volume":"287","author":"Chaikuad","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"20","key":"10.1016\/j.bone.2017.10.027_bb0070","doi-asserted-by":"crossref","first-page":"5364","DOI":"10.1093\/hmg\/ddu255","article-title":"ACVR1 p.Q207E causes classic fibrodysplasia ossificans progressiva and is functionally distinct from the engineered constitutively active ACVR1 p.Q207D variant","volume":"23","author":"Haupt","year":"2014","journal-title":"Hum. Mol. Genet."},{"issue":"11","key":"10.1016\/j.bone.2017.10.027_bb0075","first-page":"3462","article-title":"The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization","volume":"119","author":"Shen","year":"2009","journal-title":"J. Clin. Invest."},{"issue":"50","key":"10.1016\/j.bone.2017.10.027_bb0080","doi-asserted-by":"crossref","first-page":"15438","DOI":"10.1073\/pnas.1510540112","article-title":"Neofunction of ACVR1 in fibrodysplasia ossificans progressiva","volume":"112","author":"Hino","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"7","key":"10.1016\/j.bone.2017.10.027_bb0085","doi-asserted-by":"crossref","first-page":"4883","DOI":"10.1074\/jbc.M111023200","article-title":"Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter","volume":"277","author":"Korchynskyi","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"8","key":"10.1016\/j.bone.2017.10.027_bb0090","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1002\/jbmr.1637","article-title":"An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva","volume":"27","author":"Chakkalakal","year":"2012","journal-title":"J. Bone Miner. Res."},{"issue":"5","key":"10.1016\/j.bone.2017.10.027_bb0095","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/stem.1633","article-title":"Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification","volume":"32","author":"Culbert","year":"2014","journal-title":"Stem Cells"},{"key":"10.1016\/j.bone.2017.10.027_bb0100","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/1471-2121-8-41","article-title":"A rapid and sensitive bioassay to measure bone morphogenetic protein activity","volume":"8","author":"Zilberberg","year":"2007","journal-title":"BMC Cell Biol."},{"issue":"6","key":"10.1016\/j.bone.2017.10.027_bb0105","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1359\/jbmr.091110","article-title":"ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation","volume":"25","author":"van Dinther","year":"2010","journal-title":"J. Bone Miner. Res."},{"issue":"29","key":"10.1016\/j.bone.2017.10.027_bb0110","doi-asserted-by":"crossref","first-page":"22542","DOI":"10.1074\/jbc.M109.094557","article-title":"Molecular consequences of the ACVR1(R206H) mutation of fibrodysplasia ossificans progressiva","volume":"285","author":"Song","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"2\u20134","key":"10.1016\/j.bone.2017.10.027_bb0115","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000324230","article-title":"In vitro analyses of the dysregulated R206H ALK2 kinase-FKBP12 interaction associated with heterotopic ossification in FOP","volume":"194","author":"Groppe","year":"2011","journal-title":"Cells Tissues Organs"},{"issue":"8","key":"10.1016\/j.bone.2017.10.027_bb0120","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1089\/ten.2006.12.2215","article-title":"Osteogenic differentiation of mouse embryonic stem cells and mouse embryonic fibroblasts in a three-dimensional self-assembling peptide scaffold","volume":"12","author":"Garreta","year":"2006","journal-title":"Tissue Eng."},{"issue":"6","key":"10.1016\/j.bone.2017.10.027_bb0125","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1128\/MCB.02207-06","article-title":"Pref-1 (preadipocyte factor 1) activates the MEK\/extracellular signal-regulated kinase pathway to inhibit adipocyte differentiation","volume":"27","author":"Kim","year":"2007","journal-title":"Mol. Cell. Biol."},{"issue":"3","key":"10.1016\/j.bone.2017.10.027_bb0130","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/jcp.20118","article-title":"Primary mouse embryonic fibroblasts: a model of mesenchymal cartilage formation","volume":"200","author":"Lengner","year":"2004","journal-title":"J. Cell. Physiol."},{"issue":"2","key":"10.1016\/j.bone.2017.10.027_bb0135","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s12015-011-9315-x","article-title":"Mouse embryonic fibroblasts (MEF) exhibit a similar but not identical phenotype to bone marrow stromal stem cells (BMSC)","volume":"8","author":"Saeed","year":"2012","journal-title":"Stem Cell Rev."},{"issue":"10","key":"10.1016\/j.bone.2017.10.027_bb0140","first-page":"2879","article-title":"Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine\/threonine kinase activity","volume":"8","author":"ten Dijke","year":"1993","journal-title":"Oncogene"},{"issue":"3","key":"10.1016\/j.bone.2017.10.027_bb0145","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cytogfr.2005.01.009","article-title":"BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk","volume":"16","author":"Miyazono","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"issue":"5","key":"10.1016\/j.bone.2017.10.027_bb0150","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/jbmr.5650090510","article-title":"Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fracture healing","volume":"9","author":"Nakase","year":"1994","journal-title":"J. Bone Miner. Res."},{"issue":"5","key":"10.1016\/j.bone.2017.10.027_bb0155","doi-asserted-by":"crossref","first-page":"C1087","DOI":"10.1152\/ajpcell.00388.2009","article-title":"Inefficient skeletal muscle repair in inhibitor of differentiation knockout mice suggests a crucial role for BMP signaling during adult muscle regeneration","volume":"298","author":"Clever","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"issue":"12","key":"10.1016\/j.bone.2017.10.027_bb0160","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/BOT.0b013e3182712adf","article-title":"Fibroregulation of mesenchymal progenitor cells by BMP-4 after traumatic muscle injury","volume":"26","author":"Kluk","year":"2012","journal-title":"J. Orthop. Trauma"},{"key":"10.1016\/j.bone.2017.10.027_bb0165","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12964-015-0104-z","article-title":"Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B","volume":"13","author":"Olsen","year":"2015","journal-title":"Cell Commun. Signal"},{"issue":"4","key":"10.1016\/j.bone.2017.10.027_bb0170","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/0092-8674(93)90488-C","article-title":"Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors","volume":"75","author":"Attisano","year":"1993","journal-title":"Cell"},{"issue":"12","key":"10.1016\/j.bone.2017.10.027_bb0175","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1016\/j.cellsig.2013.09.002","article-title":"Activins bind and signal via bone morphogenetic protein receptor type II (BMPR2) in immortalized gonadotrope-like cells","volume":"25","author":"Rejon","year":"2013","journal-title":"Cell. Signal."},{"issue":"1\u20132","key":"10.1016\/j.bone.2017.10.027_bb0180","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2011.06.030","article-title":"New insights into the mechanisms of activin action and inhibition","volume":"359","author":"Walton","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"issue":"13","key":"10.1016\/j.bone.2017.10.027_bb0185","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1093\/emboj\/16.13.3866","article-title":"Mechanism of TGFbeta receptor inhibition by FKBP12","volume":"16","author":"Chen","year":"1997","journal-title":"EMBO J."},{"issue":"3","key":"10.1016\/j.bone.2017.10.027_bb0190","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0092-8674(00)80555-3","article-title":"Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12","volume":"96","author":"Huse","year":"1999","journal-title":"Cell"},{"issue":"3","key":"10.1016\/j.bone.2017.10.027_bb0195","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1097-2765(01)00332-X","article-title":"The TGF beta receptor activation process: an inhibitor- to substrate-binding switch","volume":"8","author":"Huse","year":"2001","journal-title":"Mol. Cell"},{"issue":"36","key":"10.1016\/j.bone.2017.10.027_bb0200","doi-asserted-by":"crossref","first-page":"21687","DOI":"10.1074\/jbc.271.36.21687","article-title":"Characterization of the interaction of FKBP12 with the transforming growth factor-beta type I receptor in vivo","volume":"271","author":"Okadome","year":"1996","journal-title":"J. Biol. Chem."},{"issue":"3","key":"10.1016\/j.bone.2017.10.027_bb0205","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0092-8674(00)80116-6","article-title":"The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors","volume":"86","author":"Wang","year":"1996","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.bone.2017.10.027_bb0210","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/dvdy.22779","article-title":"Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva","volume":"241","author":"Le","year":"2012","journal-title":"Dev. Dyn."},{"issue":"12","key":"10.1016\/j.bone.2017.10.027_bb0215","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1128\/MCB.01595-12","article-title":"Constitutively active ALK2 receptor mutants require type II receptor cooperation","volume":"33","author":"Bagarova","year":"2013","journal-title":"Mol. Cell. Biol."},{"issue":"5155","key":"10.1016\/j.bone.2017.10.027_bb0220","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1126\/science.8140412","article-title":"Characterization of type I receptors for transforming growth factor-beta and activin","volume":"264","author":"ten Dijke","year":"1994","journal-title":"Science (New York, N.Y.)"},{"issue":"5","key":"10.1016\/j.bone.2017.10.027_bb0225","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/ncb1870","article-title":"Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis","volume":"11","author":"Little","year":"2009","journal-title":"Nat. Cell Biol."},{"issue":"5112","key":"10.1016\/j.bone.2017.10.027_bb0230","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1126\/science.8388127","article-title":"Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor","volume":"260","author":"Ebner","year":"1993","journal-title":"Science (New York, N.Y.)"},{"issue":"5135","key":"10.1016\/j.bone.2017.10.027_bb0235","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1126\/science.8235612","article-title":"Determination of type I receptor specificity by the type II receptors for TGF-beta or activin","volume":"262","author":"Ebner","year":"1993","journal-title":"Science (New York, N.Y.)"}],"container-title":["Bone"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328217303939?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328217303939?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T05:42:06Z","timestamp":1719553326000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S8756328217303939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":47,"alternative-id":["S8756328217303939"],"URL":"https:\/\/doi.org\/10.1016\/j.bone.2017.10.027","relation":{},"ISSN":["8756-3282"],"issn-type":[{"value":"8756-3282","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Variable signaling activity by FOP ACVR1 mutations","name":"articletitle","label":"Article Title"},{"value":"Bone","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bone.2017.10.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}