{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:05:53Z","timestamp":1792829153507,"version":"4.5.0"},"reference-count":74,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"757","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,7,24]]},"abstract":"<jats:p>\n            Heterotopic ossification (HO), defined as the formation of extraskeletal bone in muscle and soft tissues, is a diverse pathological process caused by either genetic mutations or inciting trauma. Fibrodysplasia ossificans progressiva (FOP) is a genetic form of HO caused by mutations in the bone morphogenetic protein (BMP) type I receptor gene\n            <jats:italic>activin A receptor type 1<\/jats:italic>\n            (\n            <jats:italic>ACVR1<\/jats:italic>\n            ). These mutations make ACVR1 hypersensitive to BMP and responsive to activin A. Hedgehog (Hh) signaling also contributes to HO development. However, the exact pathophysiology of how skeletogenic cells contribute to endochondral ossification in FOP remains unknown. Here, we showed that the wild-type or FOP-mutant ACVR1 localized in the cilia of stem cells from human exfoliated deciduous teeth with key FOP signaling components, including activin A receptor type 2A\/2B, SMAD family member 1\/5, and FK506-binding protein 12kD. Cilia suppression by deletion of\n            <jats:italic>intraflagellar transport 88<\/jats:italic>\n            or\n            <jats:italic>ADP ribosylation factor like GTPase 3<\/jats:italic>\n            effectively inhibited pathological BMP and Hh signaling, subdued aberrant chondro-osteogenic differentiation in primary mouse or human FOP cells, and diminished in vivo extraskeletal ossification in\n            <jats:italic>\n              Acvr1\n              <jats:sup>Q207D<\/jats:sup>\n            <\/jats:italic>\n            ,\n            <jats:italic>Sox2-Cre<\/jats:italic>\n            ;\n            <jats:italic>\n              Acvr1\n              <jats:sup>R206H\/+<\/jats:sup>\n            <\/jats:italic>\n            FOP mice and in burn tenotomy\u2013treated wild-type mice. Our results provide a rationale for early and localized suppression of cilia in affected tissues after injury as a therapeutic strategy against either genetic or acquired HO.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abn3486","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T17:58:36Z","timestamp":1721843916000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":21,"title":["Primary cilia mediate skeletogenic BMP and Hedgehog signaling in heterotopic ossification"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6405-8330","authenticated-orcid":true,"given":"Kai","family":"He","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10172"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20868"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1783"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.12.013"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1888"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801681200"},{"key":"e_1_3_2_8_2","first-page":"3462","article-title":"The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization","volume":"119","author":"Shen Q.","year":"2009","unstructured":"Q. 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