Figure 3

PTHrP signaling pathways during endochondral ossification. (A) Indian hedgehog (Ihh)-parathyroid hormone-related protein (PTHrP) signaling pathway during endochondral ossification. Ihh (secreted by prehypertrophic chondrocytes) stimulates PTHrP production (synthesized by proliferating chondrocytes) (a), which in turn accelerates the proliferation of periarticular chondrocytes (b) and prevents chondrocyte hypertrophy (c). In addition, Ihh could stimulate periarticular chondrocyte differentiation independent of PTHrP (d). The detailed mechanisms indicated by the red dashed box is illustrated in (B). (B) Overview of the pathways whereby PTHrP inhibits chondrocyte hypertrophy during endochondral ossification. CDK, cyclin-dependent kinase; HDAC4, histone deacetylase 4; IGF, insulin-like growth factor; MAPK, mitogen-activated protein kinase; PK, protein kinase; PP2A, protein phosphatase 2A; PTH1R, parathyroid hormone 1 receptor;.