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FGFR signaling has a key role in the formation and repair of the craniofacial skeleton. Here, we analyzed the impact of\n                    <jats:italic>Fgfr2<\/jats:italic>\n                    - and\n                    <jats:italic>Fgfr3<\/jats:italic>\n                    -activating mutations on mandibular bone formation and endochondral bone repair after non-stabilized mandibular fractures in mouse models of Crouzon syndrome (\n                    <jats:italic>Crz<\/jats:italic>\n                    ) and hypochondroplasia (\n                    <jats:italic>Hch<\/jats:italic>\n                    ). Bone mineralization of the calluses was abnormally high in\n                    <jats:italic>Crz<\/jats:italic>\n                    mice and abnormally low in\n                    <jats:italic>Hch<\/jats:italic>\n                    mice. The latter model presented pseudarthrosis and impaired chondrocyte differentiation. Spatial transcriptomic analyses of the\n                    <jats:italic>Hch<\/jats:italic>\n                    callus revealed abnormally low expression of\n                    <jats:italic>Col11, Col1a, Dmp1<\/jats:italic>\n                    genes in mature chondrocytes. We found that the expression of genes involved in autophagy and apoptosis (\n                    <jats:italic>Smad1, Comp, Birc2<\/jats:italic>\n                    ) was significantly perturbed and that the\n                    <jats:italic>Dusp3<\/jats:italic>\n                    ,\n                    <jats:italic>Dusp9<\/jats:italic>\n                    ,\n                    <jats:italic>and Socs3<\/jats:italic>\n                    genes controlling the mitogen-activated protein kinase pathway were overexpressed. Lastly, we found that treatment with a tyrosine kinase inhibitor (BGJ398, infigratinib) or a C-type natriuretic peptide (BMN111, vosoritide) fully rescued the defective endochondral bone repair observed in\n                    <jats:italic>Hch<\/jats:italic>\n                    mice. Taken as a whole, our findings show that FGFR3 is a critical orchestrator of bone repair and provide a rationale for the development of potential treatments for patients with FGFR3-osteochondrodysplasia.\n                  <\/jats:p>","DOI":"10.1038\/s41413-024-00385-x","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T02:02:10Z","timestamp":1737424930000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["FGFR antagonists restore defective mandibular bone repair in a mouse model of osteochondrodysplasia"],"prefix":"10.1038","volume":"13","author":[{"given":"Anne","family":"Morice","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"de La Seigli\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Kany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman H.","family":"Khonsari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morad","family":"Bensidhoum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Emilia","family":"Puig-Lombardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-5856","authenticated-orcid":false,"given":"Laurence","family":"Legeai Mallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"385_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/wdev.176","volume":"4","author":"DM Ornitz","year":"2015","unstructured":"Ornitz, D. 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