線維芽細胞増殖因子受容体の変異と骨系統疾患(若野洋一歯科臨床医学奨励賞受賞講演)

概要

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Mutations of the human fibroblast growth factor receptors (FGFRs) have been identified to be the cause of a number of craniosynostosis syndromes such as Crouzon, Pfeiffer, Jackson-Weiss, Apert, Beare-Stevenson, and Muenke syndromes. The importance of FGFs/FGFR2 signaling in the cranial suture and limb bud development has been widely reported. It is postulated that FGFR2 signaling is essential for osteogenic cell differentiation and proliferation during the process of suture growth and closure because FGFR2 transcripts are expressed at the osteogenic fronts in developing calvarial bone. So, the mutation of FGFR may stimulate differentiation and/or proliferation in osteoblasts. We have recently reported an abnormal rapid mineralization of the callus during distraction osteogenesis of the deformed thumb in an Apert syndrome patient. Consistent with the previous genetic and biochemical studies, these clinical findings have raised a possibility that the S252W mutation of the FGFR2 may directly cause the unusual differentiation of the bone cells. These results provide that activation of FGFR2IIIc caused by the S252W mutation promotes osteoblast phenotype and that a soluble form of FGFR2 with S252W mutation controls osteoblast differentiation.