{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:33:39Z","timestamp":1757705619880},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T00:00:00Z","timestamp":1092009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Unregulated fibroblast growth factor 2 (FGF2) signaling caused by mutations in the fibroblast growth factor receptor (FGFR2) leads to human craniosynostosis such as the Apert syndrome. In an in vitro control model of calvarial osteoblasts from Apert patients carrying the FGFR2 P253R mutation, we studied the changes in cellular phenotype and evaluated the effects of FGF2. Compared with wild\u2010type controls, osteocalcin mRNA was down\u2010regulated in Apert osteoblasts, Runt\u2010related transcription factor\u20102 (RUNX2) mRNA was differentially spliced, and FGF2 secretion was greater. Total protein synthesis, fibronectin and type I collagen secretion were up\u2010regulated, while protease and glycosidase activities and matrix metalloproteinase\u201013 (MMP\u201013) transcription were decreased, suggesting an altered ECM turnover. Adding FGF2 increased protease and glycosidase activities and down\u2010regulated fibronectin and type I collagen secretion in Apert osteoblasts. High affinity FGF2 receptors were up\u2010regulated in Apert osteoblasts and analysis of signal transduction showed elevated levels of Grb2 tyrosine phosphorylation and the Grb2\u2010p85 beta association, which FGF2 stimulation strongly reduced. All together these findings suggest increased constitutive receptor activity in Apert mutant osteoblasts and an autocrine loop involving the FGF2 pathway in modulation of Apert osteoblast behavior. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.20148","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T22:29:44Z","timestamp":1092090584000},"page":"524-535","source":"Crossref","is-referenced-by-count":29,"title":["P253R fibroblast growth factor receptor\u20102 mutation induces RUNX2 transcript variants and calvarial osteoblast 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