Figure 3.

Regulation of parathyroid hormone–related protein (PTHrP)/Indian hedgehog (Ihh) signaling and fibroblast growth factor receptor 3 (FGFR3) signaling on cranial synchondrosis development. (A) PTHrP can maintain chondrocyte proliferation and inhibit their hypertrophic differentiation. Ihh promotes chondrocyte proliferation and maturation and also stimulates PTHrP expression. It is unclear whether Ihh stimulates PTHrP expression as in the growth plate of long bones. (B) Active mutation of FGFR3 suppresses chondrocyte proliferation and down-regulates expression of the PTHrP receptor and Ihh. Premature fusion of synchondroses in FGFR3 mutant mice may be mediated by the mitogen-activated protein kinase (MAPK) pathway.