title: Acid and base effects on avian osteoclast activity.
abstract: 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-].
authors.affiliation: Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri.
authors.forename: A
authors.initials: A
authors.lastname: Carano
authors.forename: P H
authors.initials: PH
authors.lastname: Schlesinger
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
authors.forename: S L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: H C
authors.initials: HC
authors.lastname: Blair
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001862:Bone Resorption; D002245:Carbon Dioxide / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology; D011200:Poultry; D051381:Rats
chemical_list: D001639:Bicarbonates; D005452:Fluoresceins; D002245:Carbon Dioxide; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein