Endocrinology, Vol 119, 119-124, Copyright © 1986 by Endocrine Society

ARTICLES

Effect of pH on bone resorption by rat osteoclasts in vitro

TR Arnett and DW Dempster

Acidosis has been implicated in the pathogenesis of various metabolic bone diseases. Experimental acid ingestion is known to stimulate the release of bone mineral in humans and increase osteoclastic resorption surfaces in animals, but the mechanism has remained unclear. We have investigated the effect of medium pH on osteoclastic activity in vitro using a new method that allows direct measurement of bone resorption. Osteoclasts were disaggregated from neonatal rat long bones and allowed to settle onto thin slices of bovine cortical bone. After 24-h incubation in medium 199, adjusted to the required pH, bone slices were fixed, and the number and surface area of resorption pits per slice were determined. Reduction in medium pH from 7.4 to 6.8 resulted in a 14-fold increase in the mean area resorbed per bone slice (P less than 0.01). Five- and 9-fold increases were seen at pH 7.2 and 7.0, respectively. Incubation of bone cells with human PTH-(1-34) (100 ng/ml) did not significantly enhance resorption at either pH 7.4 or 6.4, whereas human calcitonin (50 pg/ml) produced near-total inhibition. Mean osteoclast and mononuclear cell numbers were unaltered by all treatments. This is the first direct demonstration that low pH stimulates cell-mediated bone resorption, an observation that may have considerable physiological and pathophysiological significance.

This article has been cited by other articles:

				E. Wynn, S. A. Lanham-New, M.-A. Krieg, D. R. Whittamore, and P. Burckhardt Low Estimates of Dietary Acid Load Are Positively Associated with Bone Ultrasound in Women Older Than 75 Years of Age with a Lifetime Fracture J. Nutr., July 1, 2008; 138(7): 1349 - 1354. [Abstract] [Full Text] [PDF]

				T. R. Arnett Extracellular pH Regulates Bone Cell Function J. Nutr., February 1, 2008; 138(2): 415S - 418S. [Abstract] [Full Text] [PDF]

				S. A. Lanham-New The Balance of Bone Health: Tipping the Scales in Favor of Potassium-Rich, Bicarbonate-Rich Foods J. Nutr., January 1, 2008; 138(1): 172S - 177S. [Abstract] [Full Text] [PDF]

				S. A Lanham-New Fruit and vegetables: the unexpected natural answer to the question of osteoporosis prevention? Am. J. Clinical Nutrition, June 1, 2006; 83(6): 1254 - 1255. [Full Text] [PDF]

				K. Fuller, B. Kirstein, and T. J. Chambers Murine Osteoclast Formation and Function: Differential Regulation by Humoral Agents Endocrinology, April 1, 2006; 147(4): 1979 - 1985. [Abstract] [Full Text] [PDF]

				G. J. Spencer, J. C. Utting, S. L. Etheridge, T. R. Arnett, and P. G. Genever Wnt signalling in osteoblasts regulates expression of the receptor activator of NF{kappa}B ligand and inhibits osteoclastogenesis in vitro J. Cell Sci., April 1, 2006; 119(7): 1283 - 1296. [Abstract] [Full Text] [PDF]

				J.-P. Bonjour Dietary Protein: An Essential Nutrient For Bone Health J. Am. Coll. Nutr., December 1, 2005; 24(suppl_6): 526S - 536S. [Abstract] [Full Text] [PDF]

				S. R. Zwart, J. E. Davis-Street, D. Paddon-Jones, A. A. Ferrando, R. R. Wolfe, and S. M. Smith Amino acid supplementation alters bone metabolism during simulated weightlessness J Appl Physiol, July 1, 2005; 99(1): 134 - 140. [Abstract] [Full Text] [PDF]

				H. M Macdonald, S. A New, W. D Fraser, M. K Campbell, and D. M Reid Low dietary potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women Am. J. Clinical Nutrition, April 1, 2005; 81(4): 923 - 933. [Abstract] [Full Text] [PDF]

				S. V. Komarova, A. Pereverzev, J. W. Shum, S. M. Sims, and S. J. Dixon Convergent signaling by acidosis and receptor activator of NF-{kappa}B ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts PNAS, February 15, 2005; 102(7): 2643 - 2648. [Abstract] [Full Text] [PDF]

				S. R Zwart, A. R Hargens, and S. M Smith The ratio of animal protein intake to potassium intake is a predictor of bone resorption in space flight analogues and in ambulatory subjects Am. J. Clinical Nutrition, October 1, 2004; 80(4): 1058 - 1065. [Abstract] [Full Text] [PDF]

				S. A New, H. M MacDonald, M. K Campbell, J. C Martin, M. J Garton, S. P Robins, and D. M Reid Lower estimates of net endogenous noncarbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women Am. J. Clinical Nutrition, January 1, 2004; 79(1): 131 - 138. [Abstract] [Full Text] [PDF]

				R. C. Morris Jr. and A. Sebastian Alkali Therapy In Renal Tubular Acidosis: Who Needs It? J. Am. Soc. Nephrol., August 1, 2002; 13(8): 2186 - 2188. [Full Text] [PDF]

				A. HOEBERTZ, S. MEGHJI, G. BURNSTOCK, and T. R. ARNETT Extracellular ADP is a powerful osteolytic agent: evidence for signaling through the P2Y1 receptor on bone cells FASEB J, May 1, 2001; 15(7): 1139 - 1148. [Abstract] [Full Text] [PDF]

				S. Meghji, M. S. Morrison, B. Henderson, and T. R. Arnett pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E112 - E119. [Abstract] [Full Text] [PDF]

				S. A New, S. P Robins, M. K Campbell, J. C Martin, M. J Garton, C. Bolton-Smith, D. A Grubb, S. J Lee, and D. M Reid Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health?1 Am. J. Clinical Nutrition, January 1, 2000; 71(1): 142 - 151. [Abstract] [Full Text] [PDF]

				T. L. Burgess, Y.-x. Qian, S. Kaufman, B. D. Ring, G. Van, C. Capparelli, M. Kelley, H. Hsu, W. J. Boyle, C. R. Dunstan, et al. The Ligand for Osteoprotegerin (OPGL) Directly Activates Mature Osteoclasts J. Cell Biol., May 3, 1999; 145(3): 527 - 538. [Abstract] [Full Text] [PDF]

				T. Nordstrom, L. D. Shrode, O. D. Rotstein, R. Romanek, T. Goto, J. N.M. Heersche, M. F. Manolson, G. F. Brisseau, and S. Grinstein Chronic Extracellular Acidosis Induces Plasmalemmal Vacuolar Type H+ ATPase Activity in Osteoclasts J. Biol. Chem., March 7, 1997; 272(10): 6354 - 6360. [Abstract] [Full Text] [PDF]

				A. Sebastian, S. T. Harris, J. H. Ottaway, K. M. Todd, and R. C. Morris Improved Mineral Balance and Skeletal Metabolism in Postmenopausal Women Treated with Potassium Bicarbonate N. Engl. J. Med., June 23, 1994; 330(25): 1776 - 1781. [Abstract] [Full Text]