{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:47:31Z","timestamp":1790837251921,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,5,17]],"date-time":"2012-05-17T00:00:00Z","timestamp":1337212800000},"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":[[2012,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Apert syndrome is characterized by craniosynostosis and syndactyly, and is predominantly caused by mutation of either S252W or P253W in the fibroblast growth factor receptor (FGFR) 2 gene. In this study, we characterized the effects of one of the mutations (S252W) using primary calvarial osteoblasts derived from transgenic mice, Ap\u2010Tg and sAp\u2010Tg, that expressed an Apert\u2010type mutant FGFR2 (FGFR2IIIc\u2010S252W; FGFR2IIIc\u2010Ap), and the soluble form (extracellular domain only) of the mutant FGFR2 (sFGFR2IIIc\u2010Ap), respectively. Compared to WT\u2010derived osteoblasts, osteoblasts from Ap\u2010Tg mouse showed a higher proliferative activity and enhanced differentiation, while those from sAp\u2010Tg mouse exhibited reduced potential for proliferation and osteogenic differentiation. When transplanted with \u03b2\u2010tricalcium phosphate (\u03b2\u2010TCP) granules into immunodeficient mice, Ap\u2010Tg\u2010derived osteoblasts showed a higher bone forming capacity, whereas sAp\u2010Tg\u2010derived osteoblasts were completely deficient for this phenotype. Phosphorylation of extracellular signal\u2010regulated kinase (ERK), MEK, PLC\u03b3, and p38 was increased in Ap\u2010Tg\u2010derived osteoblasts, whereas phosphorylation of these signaling molecules was reduced in sAp\u2010Tg\u2010derived osteoblasts. Interestingly, when these experiments were carried out using osteoblasts from the mice generated by crossing Ap\u2010Tg and sAp\u2010Tg (Ap\/sAp\u2010Tg), which co\u2010expressed FGFR2IIIc\u2010Ap and sFGFR2IIIc\u2010Ap, the results were comparable to those obtained from WT\u2010derived osteoblasts. Taken together, these results indicate that osteoblasts expressing FGFR2IIIc\u2010Ap proliferate and differentiate via highly activated MEK, ERK, and p38 pathways, while these pathways are suppressed in osteoblasts expressing sFGFR2IIIc\u2010Ap. Our findings also suggest that altered FGFR2IIIc signaling in osteoblasts is mostly responsible for the phenotypes seen in Apert syndrome, therefore these osteoblast cell lines are useful tools for investigating the pathogenesis of Apert syndrome. J. Cell. Physiol. 227: 3267\u20133277, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.24021","type":"journal-article","created":{"date-parts":[[2011,11,21]],"date-time":"2011-11-21T13:57:16Z","timestamp":1321883836000},"page":"3267-3277","source":"Crossref","is-referenced-by-count":28,"title":["Apert syndrome mutant FGFR2 and its soluble form reciprocally alter osteogenesis of primary calvarial 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