Figure 5

Growth plate signalling. EXT1 and EXT2 are expressed in the proliferative and transition zone [77] (Fig. 5). The HSPGs, expressed in all zones of the growth plate [67–72]. A. In the embryonic growth plate chondrocytes in the transition zone secrete IHh protein, which diffuses to its receptor Patched (Ptc) in the lateral perichondrium. Subsequently, via a yet incompletely understood mechanism, increased secretion of ParaThyroid Hormone related Protein (PTHrP, PTHlP) is induced at the apical perichondrium, which diffuses to its receptor expressed in the late proliferating chondrocytes [80]. Terminal differentiation is inhibited by direct or indirect upregulation of Bcl-2, prolonging cell survival [78]. In this way, PTHrP regulates chondrocyte differentiation by delaying the progression of chondrocytes towards the hypertrophic zone and allowing longitudinal bone growth. B. In the post-natal growth plate the signalling is confined to the growth plate [79].