Figure 8.

Schematic representation of the expression and the roles of FGF18 in osteogenesis (A) and chondrogenesis (B). The differentiation stages and domains at which Fgf18 and Fgfrs are expressed are indicated by the rectangles. (A) In calvarial osteogenesis, osteogenic mesenchymal cells, which are characterized by expression of Msx2, differentiate to osteocytes through preosteoblasts, which express Cbfa1, but not Opn and Oc, and osteoblasts, which express Cbfa1, Opn, and Oc. Fgf18 is expressed in osteogenic mesenchyme, preosteoblasts, and osteoblasts. FGF18 positively regulates the proliferation of osteogenic mesenchyme and the differentiation to osteoblasts. FGFR2c, which can bind with high affinity to FGF18 and is transiently coexpressed with FGF18, may act as a receptor for FGF18 in this process. FGFR3c may function redundantly with FGFR2c (see Discussion). (B) In chondrogenesis of the long bone, the maturation of chondrocytes takes place through resting, proliferating, prehypertrophic, and hypertrophic stages. The hypertrophic chondrocyte is finally replaced by osteoblasts, which give rise to trabecular bone. FGF18 signaling negatively regulates the proliferation and differentiation of chondrocytes. In this case, FGF18 is expressed in the perichondrium and is likely to act on chondrocytes through FGFR3c.