pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis.
We examined the effects of HCO(3)(-) and CO(2) acidosis on osteoclast-mediated Ca(2+) release from 3-day cultures of neonatal mouse calvaria. Ca(2+) release was minimal above pH 7.2 in control cultures but was stimulated strongly by the addition of small amounts of H(+) to culture medium (HCO(3)(-) acidosis). For example, addition of 4 meq/l H(+) reduced pH from 7.12 to 7.03 and increased Ca(2+) release 3.8-fold. The largest stimulatory effects (8- to 11-fold), observed with 15-16 meq/l added H(+), were comparable to the maximal Ca(2+) release elicited by 1,25-dihydroxyvitamin D(3) [1, 25(OH)(2)D(3); 10 nM], parathyroid hormone (10 nM), or prostaglandin E(2) (1 microM); the action of these osteolytic agents was attenuated strongly when ambient pH was increased from approximately 7.1 to approximately 7.3. CO(2) acidosis was a less effective stimulator of Ca(2+) release than HCO(3)(-) acidosis over a similar pH range. Ca(2+) release stimulated by HCO(3)(-) acidosis was almost completely blocked by salmon calcitonin (20 ng/ml), implying osteoclast involvement. In whole mount preparations of control half-calvaria, approximately 400 inactive osteoclast-like multinucleate cells were present; in calvaria exposed to HCO(3)(-) acidosis and to the other osteolytic agents studied, extensive osteoclastic resorption, with perforation of bones, was visible. HCO(3)(-) acidosis, however, reduced numbers of osteoclast-like cells by approximately 50%, whereas 1,25(OH)(2)D(3) treatment caused increases of approximately 75%. The results suggest that HCO(3)(-) 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.
Meghji
S
S
Oral and Maxillofacial Surgery, Eastman Dental Institute, London WC1X 8LD, United Kingdom.
Morrison
M S
MS
Henderson
B
B
Arnett
T R
TR
D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology; D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D002452:Cell Count; D015232:Dinoprostone / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010014:Osteolysis / Q000378:metabolism*; D011522:Protons; D012886:Skull / Q000166:cytology*; D019379:Teriparatide / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D002120:Calcium Channel Agonists; D011522:Protons; D019379:Teriparatide; D002245:Carbon Dioxide; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin