TY - JOUR
AU - LINKHART, THOMAS, A.
AB - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces differentiation and inhibits proliferation in many cell types including bone cells. These effects may be mediated by the modulation of the insulin-like growth factor (IGF) regulatory system. Therefore we investigated the effects of 1,25-(OH)2D3 on transcript and protein levels of both IGF-I and IGF binding proteins (IGFBPs) in clonal mouse osteoblasts. Subconfluent cultures were treated in serum-free medium with 1,25-(OH)2D3. Secreted IGF-I was measured using a RIA under conditions eliminating the interference of IGFBPs. 1,25-(OH)2D3 (10−11- 10−8m) inhibited IGF-I release in a dose dependent manner at 24 h (maximally to 30 ± 5% of control, mean ± sem of seven independent experiments). In a time course study IGF-I increased in the media of control cultures over a 48-h period, while IGF-I secretion was completely prevented from 6 h onward in 1,25-(OH)2D3 treated cultures. Northern blot analysis revealed four IGF-I transcripts of 0.9, 1.8, 4.4, and 7.5 kilobases (kb). 1,25-2D3, decreased levels of the 7.5 kb IGF-I transcript from 4–48 h, with maximal inhibition occurring at 24 h (25% of control). Western ligand blots of the culture medium demonstrated secretion of a 25-kilodalton IGFBP, which comprised ≥90% of the secreted IGFBPs. The 25-kilodalton IGFBP had previously been shown to have sequence similarity with IGFBP- 4, a binding protein which inhibits the action of IGFs on bone cells. 1,25-(OH)2D3 treatment increased secretion of IGFBP-4 up to 14-fold over 24 h. 1,25-(OH)2D3 also increased IGFBP-4 (2.2 kb) transcript levels within 30 min, with the maximal stimulation of 8-fold occurring after 8 h. [3H]Thymidine incorporation into cells was inhibited by 1,25-(OH)2D3 both under basal and serum-stimulated conditions. Our results are consistent with the hypothesis that the effects of 1,25-(OH)2D3 on osteoblast proliferation may be mediated in part by decreased levels of IGF-I and increased concentrations of inhibitory IGFBP-4. It is proposed that this alteration in the IGF system may be an important functional autocrine or paracrine switch in the transition of osteoblasts from states of proliferation to differentiation. (Endocrinology129: 3139–3146, 1991) This content is only available as a PDF. Author notes * This work was supported by grants from the Department of Veterans Affairs and from the Loma Linda University Pediatrics Research Fund. Stephen H. Scharla is recipient of a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft, Bonn, Germany (Scha 513/1–1). Copyright © 1991 by The Endocrine Society
TI - 1,25-Dihydroxyvitamin D3 Differentially Regulates the Production of Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-4 in Mouse Osteoblasts
JF - Endocrinology
DO - 10.1210/endo-129-6-3139
DA - 1991-12-01
UR - https://www.deepdyve.com/lp/oxford-university-press/1-25-dihydroxyvitamin-d3-differentially-regulates-the-production-of-D7PkKqoh1e
SP - 3139
EP - 3146
VL - 129
IS - 6
DP - DeepDyve
ER -