Emerging insights into the role of calcium ions in osteoclast regulation

Osteoclasts are exposed to unusually high, millimolar, Ca²⁺ concentrations and can 'sense' changes in their ambient Ca²⁺ concentration during resorption. This results in a sharp cystolic Ca²⁺ increase through both Ca²⁺ release and Ca²⁺ influx. The rise in cystolic Ca²⁺ is transduced finally into an inhibition of bone resorption. We have shown that a type 2 ryanodine receptor isoform, expressed uniquely in the osteoblast plasma membrane, functions as a Ca²⁺ influx channel, and possibly as a Ca²⁺ sensor. Ryanodine receptors are ordinarily microsomal membrane Ca²⁺ release channels. They have only recently been shown to be expressed a other sites, including nuclear membranes. At the latter site, ryanodine receptors gate nucleoplasmic Ca²⁺ influx. Nucleoplasmic Ca²⁺, in turn, regulates key nuclear processes, including gene expression and apoptosis. Here, we review potential mechanisms underlying the recognition, movement, and actions of Ca²⁺ in the osteoclast.