Fig. 2
From: Endochondral bone growth, bone calcium accretion, and bone mineral density: how are they related?
An overview of the regulation of growth plate chondrocyte development by secretory and transcriptional factors. Parathyroid hormone-related peptide (PTHrP) synthesized from the perichondral cells in the epiphysis and growth plate chondrocytes acts directly on PTHrP receptor in the proliferative chondrocytes to keep chondrocytes in the proliferative stage. The prehypertrophic chondrocytes express Indian hedgehog homolog (Ihh) which acts as a negative feedback regulator that suppresses its own synthesis by stimulating PTHrP production, thereby preventing further differentiation of proliferative chondrocytes. Bone morphogenetic proteins (BMPs) promote Ihh production, whereas fibroblast growth factors (FGFs) decrease Ihh production. A proper chondrocyte development also requires regulation from transcription factors, such as Sox9, Runx2, and MEF2C, which induce chondrocyte proliferation and maturation. On the other hand, chondrocyte maturation is suppressed by the enzyme HDAC4