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Parathyroid hormone-related protein (PTHrP) is secreted by the osteoblast lineage and is involved in various physiological and pathological activities of bone. However, the association between the abnormal expression of PTHrP and FD, as well as its underlying mechanism, remains unclear. In this study, we discovered that FD patient-derived bone marrow stromal cells (FD BMSCs) expressed significantly higher levels of PTHrP during osteogenic differentiation and exhibited greater proliferation capacity but impaired osteogenic ability compared to normal control patient-derived BMSCs (NC BMSCs). Continuous exogenous PTHrP exposure on the NC BMSCs promoted the FD phenotype in both in vitro and in vivo experiments. Through the PTHrP\/cAMP\/PKA axis, PTHrP could partially influence the proliferation and osteogenesis capacity of FD BMSCs via the overactivation of the Wnt\/\u03b2-Catenin signaling pathway. Furthermore, PTHrP not only directly modulated cAMP\/PKA\/CREB transduction but was also demonstrated as a transcriptional target of CREB. This study provides novel insight into the possible pathogenesis involved in the FD phenotype and enhances the understanding of its molecular signaling pathways, offering theoretical evidence for the feasibility of potential therapeutic targets for FD.<\/jats:p>","DOI":"10.3390\/ijms24087616","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T03:01:48Z","timestamp":1682046108000},"page":"7616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PTHrP Modulates the Proliferation and Osteogenic Differentiation of Craniofacial Fibrous Dysplasia-Derived BMSCs"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8404-1667","authenticated-orcid":false,"given":"Lihang","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linhai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China"},{"name":"First Clinical Division, Peking University School and Hospital of Stomatology, Beijing 100034, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1002\/lary.28529","article-title":"Fibro-osseous Lesions of Paranasal Sinus and Craniofacial Region: A Retrospective Study of 282 Cases","volume":"131","author":"Dong","year":"2021","journal-title":"Laryngoscope"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R83","DOI":"10.1530\/EJE-19-0969","article-title":"Mosaic disorders of FGF23 excess: Fibrous dysplasia\/McCune\u2013Albright syndrome and cutaneous skeletal hypophosphatemia syndrome","volume":"182","author":"Ovejero","year":"2020","journal-title":"Eur. 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