The role of the calcium-sensing receptor in longitudinal bone growth

In 1997, W. Chang and colleagues detected the expression of calcium-sensing receptors (CaRs) in articular and growth plate cartilage. They observed that a high extracellular calcium concentration suppresses cartilage nodule formation and matrix production in chondrogenic cell lines. Based on these findings, I hypothesized that the CaR in growth plate cartilage will be activated at increasing concentrations of extracellular calcium causing inhibition of longitudinal bone growth. To test this hypothesis, fetal rat metatarsals on embryonic day 20 were cultured in serum-free medium with 0.3-3 mM calcium (Ca$\sp{2+}$) or 100 $\mu$M gadolinium (Gd$\sp{3+}$). This organ culture system was chosen over cell culture in order to maintain cellular interactions within the growth plate. I assessed the effects of these ions on the rate of longitudinal bone growth, cell proliferation, and quantitative histology. Increased extracellular calcium concentration decreased chondrocyte proliferation and hypertrophy, but increased ossification. This caused suppression of longitudinal bone growth. Thus, CaR may be a physiological regulator of bone growth, inhibiting chondrogenesis and activating ossification.