Insulin-like growth factor I rapidly enhances acid efflux from osteoblastic cells

Insulin-like growth factor I (IGF-I) is thought to stimulate bone resorptio n indirectly through a primary effect on osteoblasts, which in turn activat e osteoclasts by as-yet-unidentified mechanisms. Small decreases in extrace llular pH (pH(o)) dramatically increase the resorptive activity of osteocla sts. Our purpose was to characterize the effect of IGF-I on acid production by osteoblastic cells. When confluent, UMR-106 osteoblast-like cells and r at calvarial cells acidified the compartment beneath them. Superfusion with IGF-I caused a further decrease in pH(o). To investigate the mechanism, we monitored acid efflux from subconfluent cultures. IGF-I rapidly increased net efflux of H+ equivalents in a concentration-dependent manner. IGF-II (1 0 nM) evoked a smaller response than IGF-I (10 nM). The response to IGF-I w as partially dependent on extracellular Na+, but not glucose, and exhibited little if any desensitization. Wortmannin, an inhibitor of phosphatidylino sitol 3-kinase, abolished the response to IGF-I but not to parathyroid horm one. Thus IGF-I enhances acid efflux from osteoblastic cells, via a signali ng pathway dependent on activation of phosphatidylinositol 3-kinase. In viv o, acidification of the compartment between the osteogenic cell layer and t he bone matrix may affect diverse processes, including mineralization and o steoclastic bone resorption.