title: Differential regulation of insulin-like growth factor-I (IGF-I) and IGF-II release from cultured neonatal mouse calvaria by parathyroid hormone, transforming growth factor-beta, and 1,25-dihydroxyvitamin D3.
abstract: In a previous study we found that PTH stimulated bone resorption and release of insulin-like growth factor-I (IGF-I) and IGF-II from cultured neonatal mouse calvaria. Since IGF-I and IGF-II stimulate osteoblast proliferation and collagen synthesis, these results suggested that increased release of IGFs during resorption could mediate in part coupling of bone formation to bone resorption. In the present study two other osteolytic agents, transforming growth factor-beta (TGF beta) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3 were examined for effects on IGF release from neonatal mouse calvaria. Like PTH, TGF beta stimulated resorption and increased release of IGF-I and IGF-II. 1,25-(OH)2D3, however, stimulated resorption and IGF-II release comparable to PTH, but inhibited release of IGF-I. 1,25-(OH)2D3 (0.1-100 nM) inhibited basal release of IGF-I, and 10 nM 1,25-(OH)2D3 inhibited release of IGF-I induced by PTH or TGF beta. The effects of 1,25-(OH)2D3 were specific to this vitamin D metabolite and did not occur with 25-hydroxyvitamin D3 or 24,25-(OH)2D3 at the same concentration. Calcitonin (50 mU/ml) decreased 1,25-(OH)2D3 stimulation of resorption, but did not affect 1,25-(OH)2D3 stimulation of IGF-II release and inhibition of IGF-I release. This evidence that effects of 1,25-(OH)2D3 on release of the IGFs were independent of bone resorption supports the conclusion that 1,25-(OH)2D3 modulated the production and secretion of IGF-I and IGF-II in calvarial cells. The results of this and the previous study suggest that PTH, TGF beta, and 1,25-(OH)2D3 differentially regulate mouse calvarial cell IGF-I and IGF-II production.
authors.affiliation: Department of Biochemistry, Loma Linda University School of Medicine, California.
authors.forename: T A
authors.initials: TA
authors.lastname: Linkhart
authors.forename: M J
authors.initials: MJ
authors.lastname: Keffer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D003470:Culture Media; D046508:Culture Techniques; D006887:Hydroxycholecalciferols / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009994:Osmolar Concentration; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012886:Skull / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002116:Calcitonin; D002117:Calcitriol