Abstract
During endo chondral bone development, parathyroid hormone-related peptide(PTHrP)is expressed by the perichondrial cells and proliferating chondrocytes in the periarticular region. PTHrP mRNA expression is increased by Indian Hedgehog(Ihh), which is expressed by prehypertrophic and hypertrophic chondrocytes. PTHrP acts directly on columnar proliferating chondrocytes to prevent hypertrophic differentiation. This prevention indirectly results in less Ihh signaling by decreasing the number of prehypertrophic and hypertrophic chondrocytes expressing Ihh. This negative feedback loop serves to regulate the balance of differentiation and proliferation of growth plate chondrocytes. Gs, cAMP, Sox9 and CREB seem to act downstream of PTHrP, while Patched, smoothened, Gli appear to act downstream of Ihh.
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