Macrophage-mediated bone resorption occurs in an acidic environment

Summary Resorption is a continuous skeletal process involving the degratation of both the organic and inorganic matrices of bone. This process has received much attention, but little is known about the physical mechanism by which resorptive cells degrade the skeleton. In this study, we examined the pH at the resorptive cell-bone interface using a fluorescent dye, fluorescein isothiocyanate, conjugated to the organic matrix of devitalized rat bone. Because the visible spectrum of fluorescein differs in acidic and neutral environments, the relative magnitudes of fluorescence at two different wave lengths indicates whether the pH at the fluorescing site is above or below the pKa of the dye. Our studies indicate that macrophage-mediated bone resorption occurs at pH below 6.0. The presence of parathyroid hormone or calcitonin, however, has no effect on the cell-matrix interface pH after 6 hours of incubation. In contrast to resorptive macrophages, fibroblasts, which bind to bone without resorbing it, do not generate an acidic environment at the matrix attachment site. This work was supported in part by NIH Grant No. AM32788 and by a Nenezian donation.