Advertisement

Citations to this article

Abstract

Osteoclasts resorb bone by first attaching to the bone surface and then secreting protons into an isolated extracellular compartment formed at the cell-bone attachment site. This secretion of protons (local acidification) is required to solubilize bone hydroxyapatite crystals and for activity of bone collagen-degrading acid proteases. However, the large quantity of protons required, 2 mol/mol of calcium, would result in an equal accumulation of cytosolic base equivalents. This alkaline load must be corrected to maintain cytosolic pH within physiologic limits. In this study, we have measured cytoplasmic pH with pH-sensitive fluorescent compounds, while varying the extracellular ionic composition of the medium, to determine the nature of the compensatory mechanism used by osteoclasts during bone resorption. Our data show that osteoclasts possess a chloride/bicarbonate exchanger that enables them to maintain normal intracellular pH in the face of a significant proton efflux. This conclusion follows from the demonstration of a dramatic cytoplasmic acidification when osteoclasts that have been incubated in bicarbonate-containing medium are transferred into bicarbonate-free medium. This acidification is absolutely dependent on and proportional to medium [Cl-]. Furthermore, acidification is inhibited by the classic inhibitor of red cell anion exchange, 4,4'-diisothiocyanatostilbene-2,2'-disulfonate, and by diphenylamine-2-carboxylate, an inhibitor of chloride specific channels. However, the acidification process is neither energy nor sodium dependent. The physiologic importance of chloride/bicarbonate exchange is demonstrated by the chloride dependence of recovery from an endogenous or exogenous alkaline load in osteoclasts. We conclude that chloride/bicarbonate exchange is in large part responsible for cytoplasmic pH homeostasis of active osteoclasts, showing that these cells are similar to renal tubular epithelial cells in their regulation of intracellular pH.

Authors

A Teti ... A Zambonin-Zallone, P H Schlesinger

×

Total citations by year

Year: 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 Total
Citations: 3 2 2 5 1 2 7 1 1 1 2 3 4 2 1 3 1 4 3 2 4 1 5 4 3 67
Citation information

Citations to this article in year 2004 (2)

Title and authors Publication Year
Osteopetrosis
J Tolar, SL Teitelbaum, PJ Orchard
Boston Medical and Surgical Journal 2004
Bone Tissue Engineering
H Donahue, E Vogler, C Siedlecki
Bone Tissue Engineering 2004

Advertisement
Advertisement