Endocrinology, Vol 137, 1921-1931, Copyright © 1996 by Endocrine Society

ARTICLES

Osteogenic protein-1-mediated insulin-like growth factor gene expression in primary cultures of rat osteoblastic cells

LC Yeh, ML Adamo, AM Kitten, MS Olson and JC Lee
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760, USA.

Osteogenic protein-1 (OP-1) is a member of the bone morphogenetic protein family and has been shown to induce new bone formation in vivo. In the present study, we determined whether the expression of the IGF system, a significant growth factor system in bone, was altered by OP-1 in primary cultures of fetal rat calvarial cells. Levels of messenger RNA (mRNA) encoding insulin-like growth factor I (IGF-I), IGF-II, IGF-I receptor, and IGF-binding proteins (IGFBP-1 to -6) were determined after OP-1 treatment. The level of total IGF-I mRNA was elevated in an OP-1 concentration (0-1000 ng/ml)-dependent manner, with maximal stimulation of IGF-I mRNA of 2- to 3-fold apparent 24 h after treatment. The increase in the IGF-I mRNA level involved a preferential stimulation of transcripts initiated at start site 2 in the exon 1 promoter. The level of IGF-II mRNA also increased by approximately 2- fold in OP-1 treated cells in a concentration-dependent manner. The level of IGF-I receptor mRNA was not altered by treatment. Whereas IGFBP-1 mRNA was not detected in these cells, IGFBP-2 mRNA was expressed, but the expression was not changed after treatment for 48 h in the concentration range (0-1000 ng/ml) tested. The IGFBP-3 mRNA level was increased slightly 48 h after OP-1 treatment in a concentration-dependent manner. The IGFBP-4, -5, and -6 mRNA levels decreased dramatically in an OP-1 concentration-dependent manner. In addition, coincubation of antisense oligonucleotides corresponding to IGF-I or -II mRNA sequence with OP-1 reduced the OP-1 induced elevation in alkaline phosphatase activity. The present results suggest that the differentiation of rat osteoblastic cells in response to OP-1 is mediated in part by increased IGF-I -II gene expression and alterations in the gene expression of different IGFBPs.

This article has been cited by other articles:

				H.-J. Im, C. Pacione, S. Chubinskaya, A. J. van Wijnen, Y. Sun, and R. F. Loeser Inhibitory Effects of Insulin-like Growth Factor-1 and Osteogenic Protein-1 on Fibronectin Fragment- and Interleukin-1{beta}-stimulated Matrix Metalloproteinase-13 Expression in Human Chondrocytes J. Biol. Chem., July 3, 2003; 278(28): 25386 - 25394. [Abstract] [Full Text] [PDF]

				L.-C. C. Yeh and J. C. Lee Identification of an Osteogenic Protein-1 (Bone Morphogenetic Protein-7)-Responsive Element in the Promoter of the Rat Insulin-Like Growth Factor-Binding Protein-5 Gene Endocrinology, September 1, 2000; 141(9): 3278 - 3286. [Abstract] [Full Text] [PDF]

				L.-C. C. Yeh, M. L. Adamo, M. S. Olson, and J. C. Lee Osteogenic Protein-1 and Insulin-Like Growth Factor I Synergistically Stimulate Rat Osteoblastic Cell Differentiation and Proliferation Endocrinology, October 1, 1997; 138(10): 4181 - 4190. [Abstract] [Full Text] [PDF]

				J. M. Hayden, D. D. Strong, D. J. Baylink, D. R. Powell, T. K. Sampath, and S. Mohan Osteogenic Protein-1 Stimulates Production of Insulin-Like Growth Factor Binding Protein-3 Nuclear Transcripts in Human Osteosarcoma Cells Endocrinology, October 1, 1997; 138(10): 4240 - 4247. [Abstract] [Full Text] [PDF]