Figure 2. Signaling pathways in the postnatal growth plate.

A. During endochondral bone development, FGF9 and FGF18, derived from the perichondrium and surrounding tissue, signal to FGFR3 in chondrocytes. The balance of chondrocyte proliferation and differentiation is controlled by crosstalk of several signaling pathways. Expression of FGFR3 is enhanced by thyroid hormone (T₃) and suppressed by PTHLH. FGFR3 signaling results in increased expression of Snail1, which is required for activation of STAT1 and MAPK signaling. Signaling from PTHLH, IHH and BMPs antagonizes the suppression of chondrocyte proliferation by FGFR3. Both FGFR3 and PTHLH function to suppress chondrocyte differentiation and antagonize the action of Wnt signaling, which promotes differentiation. FGFR3 negatively regulates the autophagy protein, ATG5. B. Activation of downstream signals, PP2a and STAT1, regulate p107, p21^Waf1/Cip1 activation, respectively, which function to suppress chondrocyte proliferation. Activation of the MAPKs, ERK1 and ERK2, regulate Sox9 expression, which functions to suppress chondrocyte terminal differentiation and endochondral ossification.