title: Insulin-like growth factor I rapidly enhances acid efflux from osteoblastic cells.
abstract: Insulin-like growth factor I (IGF-I) is thought to stimulate bone resorption indirectly through a primary effect on osteoblasts, which in turn activate osteoclasts by as-yet-unidentified mechanisms. Small decreases in extracellular pH (pHo) dramatically increase the resorptive activity of osteoclasts. Our purpose was to characterize the effect of IGF-I on acid production by osteoblastic cells. When confluent, UMR-106 osteoblast-like cells and rat calvarial cells acidified the compartment beneath them. Superfusion with IGF-I caused a further decrease in pHo. 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 (10 nM) evoked a smaller response than IGF-I (10 nM). The response to IGF-I was partially dependent on extracellular Na+, but not glucose, and exhibited little if any desensitization. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, abolished the response to IGF-I but not to parathyroid hormone. Thus IGF-I enhances acid efflux from osteoblastic cells, via a signaling pathway dependent on activation of phosphatidylinositol 3-kinase. In vivo, acidification of the compartment between the osteogenic cell layer and the bone matrix may affect diverse processes, including mineralization and osteoclastic bone resorption.
authors.affiliation: Department of Physiology and Division of Oral Biology, School of Dentistry, Faculty of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: A
authors.initials: A
authors.lastname: Santhanagopal
authors.forename: S J
authors.initials: SJ
authors.lastname: Dixon
mesh_terms: D000143:Acids / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D017451:Receptors, Somatomedin / Q000502:physiology; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000143:Acids; D000730:Androstadienes; D004791:Enzyme Inhibitors; D005947:Glucose; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011522:Protons; D017451:Receptors, Somatomedin; D012964:Sodium; D000077191:Wortmannin