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.
D000818:Animals; D002116:Calcitonin / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015850:Interleukin-6 / Q000502:physiology; D008564:Membrane Potentials; D010010:Osteoclasts / Q000502:physiology*; D015398:Signal Transduction