Effects of parathyroid hormone-related peptide on chick growth plate chondrocytes

Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH) have similar biological effects in vitro that are mediated through the PTH receptor. PTH receptors have been demonstrated in the zone of provisional calcification and the hypertrophic zone of the cartilaginous growth plate. The current study examined the biological effects of PTHrP on chick growth plate chondrocytes. Chondrocytes were exposed to varying doses of PTHrP for 24 h, and the incorporation of radioactive thymidine into DNA was used as an index of proliferation. A dose-dependent stimulation of proliferation was seen, with a maximal 27-fold increase at 50 nM PTHrP. A dose-dependent stimulation of cAMP was seen, with a maximal effect at a dose of 50 nM. Proteoglycan synthesis, measured by incorporation of radioactive sulfate, was stimulated, with a maximal effect of 65% at 1 nM. Collagen synthesis and alkaline phosphatase activity from both cellular and matrix vesicle sources decreased in a dose-dependent fashion, with a maximal inhibition of approximately 50% of the control value. The physiologic significance of the PTH and PTHrP-responsiveness of growth plate chondrocytes is uncertain at the present time. It is possible that PTH or PTHrP, or both, act as a systemic, developmental modulator of cellular proliferation and differentiation in the growth plate.