{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:29:08Z","timestamp":1779114548606,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":328,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013117","name":"International Fibrodysplasia Ossificans Progressiva Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013117","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P01 AG062413"],"award-info":[{"award-number":["P01 AG062413"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Radiant Hope Foundation"},{"DOI":"10.13039\/100013117","name":"International Fibrodysplasia Ossificans Progressiva Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013117","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P01 AG062413"],"award-info":[{"award-number":["P01 AG062413"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by mutations in activin A receptor type I\/activin-like kinase 2 (ACVR1\/ALK2), a bone morphogenetic protein (BMP) type I receptor, resulting in the formation of extraskeletal or heterotopic ossification (HO) and other features consistent with premature aging. During the first decade of life, episodic bouts of inflammatory swellings (flare-ups) occur, which are typically triggered by soft tissue trauma. Through an endochondral process, these exacerbations ultimately result in skeletal muscles, tendons, ligaments, fascia, and aponeuroses transforming into ectopic bone, rendering movement impossible. We have previously shown that soft tissue injury causes early FOP lesions characterized by cellular hypoxia, cellular damage, and local inflammation. Here we show that muscle injury in FOP also results in senescent cell accumulation, and that senescence promotes tissue reprogramming toward a chondrogenic fate in FOP muscle but not wild-type (WT) muscle. Using a combination of senolytic drugs we show that senescent cell clearance and reduction in the senescence associated secretory phenotype (SASP) ameliorate HO in mouse models of FOP. We conclude that injury-induced senescent cell burden and the SASP contribute to FOP lesion formation and that tissue reprogramming in FOP is mediated by cellular senescence, altering myogenic cell fate toward a chondrogenic cell fate. Furthermore, pharmacological removal of senescent cells abrogates tissue reprogramming and HO formation. Here we provide proof-of-principle evidence for senolytic drugs as a future therapeutic strategy in FOP. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4458","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T10:03:13Z","timestamp":1633946593000},"page":"95-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clearance of Senescent Cells From Injured Muscle Abrogates Heterotopic Ossification in Mouse Models of Fibrodysplasia Ossificans Progressiva"],"prefix":"10.1093","volume":"37","author":[{"given":"Haitao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine Mayo Clinic College of Medicine, Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai 200025 China"},{"name":"Department of Medicine Mayo Clinic College of Medicine, Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick S.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"The Center for Research in FOP & Related Disorders The Perelman School of Medicine of The University of Pennsylvania Philadelphia PA USA"},{"name":"Department of Medicine The Perelman School of Medicine of The University of Pennsylvania Philadelphia PA USA"},{"name":"Department of Orthopaedic Surgery The Perelman School of Medicine of The University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-9438","authenticated-orcid":false,"given":"Robert J.","family":"Pignolo","sequence":"additional","affiliation":[{"name":"Department of Medicine Mayo Clinic College of Medicine, Mayo Clinic Rochester MN USA"},{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"2024012714045738900_jbmr4458-bib-0001","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1750-1172-6-80","article-title":"Fibrodysplasia ossificans progressiva: clinical and genetic aspects","volume":"6","author":"Pignolo","year":"2011","journal-title":"Orphanet J Rare Dis"},{"issue":"Suppl 2","key":"2024012714045738900_jbmr4458-bib-0002","first-page":"437","article-title":"Fibrodysplasia ossificans 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