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FD is caused by GNAS mutations that increase intracellular cAMP levels. While appendicular lesions have been extensively studied to enhance understanding and management of the disease, the pathogenesis of craniofacial lesions remains poorly described despite the embryological, phenotypic and mechanical differences between these two skeletal regions. Our objective was to evaluate the impact of craniofacial FD on bone homeostasis. Typical histological features, suh as \u201calphabet soup\u201d appearance, were observed in craniofacial FD lesions. Higher intracellular cAMP levels were also noted in FD cultures derived from craniofacial lesions. We demonstrated an increased proliferative capacity in craniofacial FD osteoblasts, associated with decreased osteoblastic differentiation and a lack in mineralization abilities. Interestingly, we highlighted a decreased osteoclastogenic potential due to impaired osteoclast formation in FD-conditioned medium cultures, indicating a diminished osteoclastogenic potential of craniofacial FD osteoblasts. Our data suggest shared characteristics between osteoblasts from the craniofacial and the appendicular skeletons but also discrepancies regarding osteoclastic potential. Exploring these features could help explain the differences observed between appendicular and cranio-facial lesions and should lead to further studies on the pathogenesis of craniofacial fibrous dysplasia.<\/jats:p>","DOI":"10.1186\/s13023-026-04262-0","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T14:54:37Z","timestamp":1771944877000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In vitro characterization of osteoblasts from craniofacial fibrous dysplasia of bone and their impact on bone homeostasis"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4469-3956","authenticated-orcid":false,"given":"Johan","family":"Sergheraert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Dumortier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Guillaume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Laurence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Bornert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie C.","family":"Gangloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Mauprivez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4826-2160","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Velard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"issue":"6","key":"4262_CR1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/j.1365-2559.2007.02676.x","volume":"50","author":"BD Idowu","year":"2007","unstructured":"Idowu BD, Al-Adnani M, O\u2019Donnell P, Yu L, Odell E, Diss T, et al. 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