Endocrinology, Vol 135, 284-289, Copyright © 1994 by Endocrine Society

ARTICLES

Regulation of insulin-like growth factor-II synthesis in bone cell cultures by skeletal growth factors

B Gabbitas, J Pash and E Canalis
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.

Insulin-like growth factor-II (IGF-II) is a growth factor secreted by bone cells and presumed to act as an autocrine regulator of bone formation. Although hormones and growth factors regulate the synthesis of skeletal IGF-I, hormones do not seem to modify the synthesis of skeletal IGF-II. We postulated that skeletal IGF-II is regulated by growth factors, and we tested the effects of basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF beta 1), and platelet-derived growth factor-BB (PDGF-BB) on IGF-II messenger RNA (mRNA) expression and polypeptide concentrations in cultures of osteoblast-enriched (Ob) cells from 22-day-old fetal rat calvariae. Steady state IGF-II mRNA levels were determined by Northern blot analysis, and IGF-II concentrations were determined in acidified and fractionated culture medium by a specific RIA. Treatment of Ob cells with bFGF, TGF beta 1, and PDGF-BB decreased IGF-II mRNA levels after 24-48 h. A continuous 48-h treatment with bFGF at 0.6-6 nM, TGF beta 1 at 0.04-1.2 nM, and PDGF-BB at 0.3-3.3 nM caused a dose-dependent decrease in steady state IGF-II mRNA. The effects of bFGF, TGF beta 1, and PDGF-BB on IGF-II mRNA were dependent on protein synthesis and decreased in the presence of cycloheximide at 3.6 microM, but were independent of cell division, because they were observed in the presence and absence of 1 mM hydroxyurea. Treatment with bFGF, TGF beta 1, and PDGF-BB for 24 h did not cause a change in IGF-II polypeptide levels. PDGF-BB at 3.3 nM and TGF beta 1 at 0.04-0.4 nM for 48 h decreased IGF-II polypeptide levels by about 50%, although bFGF had no effect. In conclusion, bFGF, TGF beta 1, and PDGF decrease skeletal IGF- II transcript levels, and this effect may contribute to their actions on selected aspects of Ob cell function.

This article has been cited by other articles:

				E. Grundberg, H. Brandstrom, K. C. L. Lam, S. Gurd, B. Ge, E. Harmsen, A. Kindmark, O. Ljunggren, H. Mallmin, O. Nilsson, et al. Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells Physiol Genomics, May 9, 2008; 33(3): 301 - 311. [Abstract] [Full Text] [PDF]

				C. Palermo, P. Manduca, E. Gazzerro, L. Foppiani, D. Segat, and A. Barreca Potentiating role of IGFBP-2 on IGF-II-stimulated alkaline phosphatase activity in differentiating osteoblasts Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E648 - E657. [Abstract] [Full Text] [PDF]

				N. Boulle, C. Gicquel, A. Logie, R. Christol, J.-J. Feige, and Y. Le Bouc Fibroblast Growth Factor-2 Inhibits the Maturation of Pro-Insulin-Like Growth Factor-II (Pro-IGF-II) and the Expression of Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) in the Human Adrenocortical Tumor Cell Line NCI-H295R Endocrinology, September 1, 2000; 141(9): 3127 - 3136. [Abstract] [Full Text] [PDF]

				B. Gabbitas and E. Canalis Insulin-like growth factors sustain insulin-like growth factor-binding protein-5 expression in osteoblasts Am J Physiol Endocrinol Metab, August 1, 1998; 275(2): E222 - E228. [Abstract] [Full Text] [PDF]

				V. Gangji, S. Rydziel, B. Gabbitas, and E. Canalis Insulin-Like Growth Factor II Promoter Expression in Cultured Rodent Osteoblasts and Adult Rat Bone Endocrinology, May 1, 1998; 139(5): 2287 - 2292. [Abstract] [Full Text] [PDF]

				N. Franchimont, V. Gangji, D. Durant, and E. Canalis Interleukin-6 with Its Soluble Receptor Enhances the Expression of Insulin-Like Growth Factor-I in Osteoblasts Endocrinology, December 1, 1997; 138(12): 5248 - 5255. [Abstract] [Full Text] [PDF]

				C. K. Ritchie, L. R. Andrews, K. G. Thomas, D. J. Tindall, and L. A. Fitzpatrick The Effects of Growth Factors Associated with Osteoblasts on Prostate Carcinoma Proliferation and Chemotaxis: Implications for the Development of Metastatic Disease Endocrinology, March 1, 1997; 138(3): 1145 - 1150. [Abstract] [Full Text] [PDF]

				E. Canalis and B. Gabbitas Skeletal Growth Factors Regulate the Synthesis of Insulin-like Growth Factor Binding Protein-5 in Bone Cell Cultures J. Biol. Chem., May 5, 1995; 270(18): 10771 - 10776. [Abstract] [Full Text] [PDF]