Subcellular regulation of the ionized calcium pool in isolated growth-plate chondrocytes

At a low total endogenous calcium content, as in the reserve and proliferative zone chondrocyte, cells buffer their ionized calcium pool at a low steady state between 150 and 300 nM. The endoplasmic reticulum appears to be primarily effective in the regulation of the ionized calcium pool under these conditions. With calcium loading of 20 to 30 nmol Ca+2/mg protein, as in the hypertrophic zone chondrocyte, the cells buffer their ionized calcium pool at a higher steady state between 600 and 700 nM. The mitochondria appear to be primarily effective in buffering the cytosolic ionized calcium pool after calcium loading. These data suggest that in the growth plate as the chondrocyte approaches the mineralization front, there is an accumulation of intracellular calcium that results in the saturation of the capacity of the endoplasmic reticulum to buffer the ionized calcium pool at a low steady state. Under these conditions of calcium loading, there is an increase in the intracellular ionized calcium concentration and a shift toward mitochondrial buffering of this calcium pool. This study has clinical relevance because in the cartilaginous tissues of the growth plate and in fracture callus, the matrix mineralizes as a prerequisite step in the formation of bone. Intracellular calcium accumulation and calcium release appear to play a role in matrix mineralization. An understanding of how the chondrocyte regulates intracellular calcium homeostasis in states of calcium accumulation is important in the overall understanding of bone development and fracture healing.