Osteoclasts generate a massive acid flux to mobilize bone calcium. Local extracellular acidification by polarized vacuolar-type H+-ATPase, balanced by contralateral HCO3/--Cl- exchange to maintain physiological intracellular pH, is theorized to drive this process. It follows that extracellular pH, PCO2, or HCO3/- concentration ([HCO3/-]) should impact bone matrix dissolution. However, the effects on bone resorption of the concentrations of these ions or their transmembrane gradients are unknown. Furthermore, because bone management is a vital process, regulatory feedback may minimize such effects. Thus a complex relationship between bone resorption and pH, PCO2, and [HCO3/-] is expected but requires experimental determination. We measured bone resorption by isolated avian osteoclasts while varying these parameters across the physiological range. Bone degradation increased 50% from pH 7.3 to 6.7, whether achieved by changing [HCO3/-] (2.3-38 mM) at constant HCO3 or PCO2 (15-190 mmHg) at constant [HCO3/-]. However, at constant pH, changing PCO2 and [HCO3/-] within physiological limits did not affect bone resorption. In contrast, total HCO3 removal at pH 7.4 reduced bone degradation by rat or avian osteoclasts substantially, confirming that normal acid secretion requires HCO3/-. These observations support a model coupling osteoclastic bone resorption to proton and HCO3/- transport but indicate that [HCO3/-] is not rate limiting under physiological conditions. Extracellular pH changes affect osteoclastic bone resorption measurably, but not dramatically, at physiological [HCO3/-].
|Journal||American Journal of Physiology - Cell Physiology|
|Issue number||3 33-3|
|State||Published - Jan 1 1993|
- bone resorption
- proton transport