{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:36:59Z","timestamp":1790681819507,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":2378,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder that is characterized by episodic yet cumulative heterotopic ossification (HO) in skeletal muscles, tendons, and ligaments over a patient's lifetime. FOP is caused by missense mutations in the type I bone morphogenetic protein (BMP) receptor ACVR1. We have determined that the formation of heterotopic bone in FOP requires activation of mutant ACVR1 by Activin A, in part by showing that prophylactic inhibition of Activin A blocks HO in a mouse model of FOP. Here we piece together a natural history of developing HO lesions in mouse FOP, and determine where in the continuum of HO Activin A is required, using imaging (T2-MRI, \u03bcCT, 18F-NaF PET\/CT, histology) coupled with pharmacologic inhibition of Activin A at different times during the progression of HO. First, we show that expansion of HO lesions comes about through growth and fusion of independent HO events. These events tend to arise within a neighborhood of existing lesions, indicating that already formed HO likely triggers the formation of new events. The process of heterotopic bone expansion appears to be dependent on Activin A because inhibition of this ligand suppresses the growth of nascent HO lesions and stops the emergence of new HO events. Therefore, our results reveal that Activin A is required at least up to the point when nascent HO lesions mineralize and further demonstrate the therapeutic utility of Activin A inhibition in FOP. These results provide evidence for a model where HO is triggered by inflammation but becomes \u201cself-propagating\u201d by a process that requires Activin A. \u00a9 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.3235","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T06:12:53Z","timestamp":1502086373000},"page":"2489-2499","source":"Crossref","is-referenced-by-count":64,"title":["The Expansion of Heterotopic Bone in Fibrodysplasia Ossificans Progressiva Is Activin A-Dependent"],"prefix":"10.1093","volume":"32","author":[{"given":"Jaymin","family":"Upadhyay","sequence":"first","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiQin","family":"Xie","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Huang","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanditha","family":"Das","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel C","family":"Stewart","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan C","family":"Lyon","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keryn","family":"Palmer","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saathyaki","family":"Rajamani","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Graul","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merryl","family":"Lobo","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J","family":"Wellman","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J","family":"Soares","sequence":"additional","affiliation":[{"name":"College of Holy CrossWorcesterMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D","family":"Silva","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Hesterman","sequence":"additional","affiliation":[{"name":"InviCRO, LLCBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xialing","family":"Wen","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Qian","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyan","family":"Nannuru","sequence":"additional","affiliation":[{"name":"Regeneron 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