{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:05:11Z","timestamp":1753877111177,"version":"3.41.2"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T00:00:00Z","timestamp":1740873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH: NIDCR","award":["640T90DE021989-09"],"award-info":[{"award-number":["640T90DE021989-09"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["M01 RR00052","R01 AR081659","R21 HD078864"],"award-info":[{"award-number":["M01 RR00052","R01 AR081659","R21 HD078864"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Thrasher Research Foundation","award":["02818-8"],"award-info":[{"award-number":["02818-8"]}]},{"name":"US Food and Drug Administration Office of Orphan Products Development","award":["R01 FD-R-003409","R01 FD-R-002568"],"award-info":[{"award-number":["R01 FD-R-003409","R01 FD-R-002568"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Heterotopic ossifications (HOs) are the pathologic process by which bone inappropriately forms outside of the skeletal system. Despite HOs being a persistent clinical problem in the general population, there are no definitive strategies for their prevention and treatment due to a limited understanding of the cellular and molecular mechanisms contributing to lesion development. One disease in which the development of heterotopic subcutaneous ossifications (SCOs) leads to morbidity is Albright hereditary osteodystrophy (AHO). Albright hereditary osteodystrophy is caused by heterozygous inactivation of GNAS, the gene that encodes the \u03b1-stimulatory subunit (G\u03b1s) of G proteins. Previously, we had shown using our laboratory\u2019s AHO mouse model that SCOs develop around hair follicles. Here we show that SCO formation occurs due to inappropriate expansion and osteogenic differentiation of cells that express alpha-smooth muscle actin and that are located within the dermal sheath. We also show in AHO patients and mice that secreted frizzled related protein 2 (SFRP2) expression is upregulated in regions of SCO formation and that elimination of Sfrp2 in male AHO mice leads to earlier development, greater severity, and acceleration of formation of SCOs. These studies provide key insights into the cellular and molecular mechanisms contributing to SCO development and have implications for potential therapeutic modalities not only for AHO patients but also for patients suffering from HOs with other etiologies.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf038","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T23:05:06Z","timestamp":1741129506000},"source":"Crossref","is-referenced-by-count":0,"title":["Alpha-smooth muscle actin-expressing dermal sheath cells are a major cellular contributor to heterotopic subcutaneous ossifications in a mouse model of Albright hereditary osteodystrophy"],"prefix":"10.1093","volume":"9","author":[{"given":"Patrick","family":"McMullan","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine , Farmington, CT 06030 ,","place":["United States"]},{"name":"Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Maye","sequence":"additional","affiliation":[{"name":"Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sierra H","family":"Root","sequence":"additional","affiliation":[{"name":"Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingfen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine , Farmington, CT 06030 ,","place":["United States"]},{"name":"Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Edie","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Farmington, CT 06032 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo","family":"Kalajzic","sequence":"additional","affiliation":[{"name":"Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-610X","authenticated-orcid":false,"given":"Emily L","family":"Germain-Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Connecticut School of Medicine , Farmington, CT 06030 ,","place":["United States"]},{"name":"Department of Reconstructive Sciences, Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030 ,","place":["United States"]},{"name":"Division of Endocrinology & Diabetes, Albright Center, Connecticut Children\u2019s , Farmington, CT 06032 ,","place":["United 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