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Activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) have previously been shown to causeskeletal dysplasias through their effect on growth plate chondrocytes. However, the effect of FGFR3 mutations onbone progenitor cells may differ. The objective of this study was to investigate the effect of specific activating FGFR3mutations on ectopic in vivo bone formation by periosteal derived cells (PDCs) seeded on calcium phosphate/collagen scaffolds.PDCs were isolated from hypochondroplasic (N540K mutation) and achondroplasic (G380R mutation)patients, along with age/sex matched controls. These cells were characterised in vitro for proliferation, osteogenicdifferentiation, FGFR3 signalling and in vivo bone formation. Subsequently, empirical modelling was used to findcorrelations between in vivo formed bone and in vitro cell behaviour. These data showed that in contrast to the G380Rmutation, which produced no bone, the N540K mutation induced significant ectopic bone formation on specificcarriers. This allowed correlation between percentage of induced bone formation to elevated in vitro proliferationand differentiation. Correlating osteogenic markers included Collagen type 1, alkaline phosphatase and osteocalcin.Enhanced proliferation was attributed to increased phosphorylation of Erk-1/2.This study highlights the importance of FGFR3 in periosteal cell differentiation and also indicates it potential fortargeted tissue engineering strategies.status: accepte

journal of tissue science and engineering

The Effect of Activating Fibroblast Growth Factor Receptor 3 Mutations on Osteogenic Differentiation and Ectopic Bone Formation by Human Periosteal Derived Cells