pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis

pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis. Am J Physiol Endocrinol Metab 280: E112-E119, 2001.--We examined the effects of [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] and [CO.sub.2] acidosis on osteoclast-mediated [Ca.sup.2+] release from 3-day cultures of neonatal mouse calvaria. [Ca.sup.2+] release was minimal above pH 7.2 in control cultures but was stimulated strongly by the addition of small amounts of [H.sup.+] to culture medium ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] acidosis. For example, addition of 4 meq/l [H.sup.+] reduced pH from 7.12 to 7.03 and increased [Ca.sup.2+] release 3.8-fold. The largest stimulatory effects (8- to 11-fold), observed with 15-16 meq/l added [H.sup.+], were comparable to the maximal [Ca.sup.2+] release elicited by 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]; 10 nM], parathyroid hormone (10 nM), or prostaglandin [E.sub.2] (1 [micro]M); the action of these osteolytic agents was attenuated strongly when ambient pH was increased from ~7.1 to -7.3. [CO.sub.2] acidosis was a less effective stimulator of [Ca.sup.2+] release than [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] acidosis over a similar pH range. [Ca.sup.2+] release stimulated by [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] acidosis was almost completely blocked by salmon calcitonin (20 ng/ml), implying osteoclast involvement. In whole mount preparations of control half-calvaria, ~400 inactive osteoclast-like multinucleate cells were present; in calvaria exposed to [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] acidosis and to the other osteolytic agents studied, extensive osteoclastic resorption, with perforation of bones, was visible. [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] acidosis, however, reduced numbers of osteoclast-like cells by ~50%, whereas 1,25[(OH).sub.2][D.sub.3] treatment caused increases of ~75%. The results suggest that [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] acidosis stimulates resorption by activating mature osteoclasts already present in calvarial bones, rather than by inducing formation of new osteoclasts, and provide further support for the critical role of acid-base balance in controlling osteoclast function. calcium release; carbon dioxide; bicarbonate ion; acid-base balance; osteolysis