Endocrinology, Vol 131, 2113-2119, Copyright © 1992 by Endocrine Society

ARTICLES

The effects of prostaglandin E2, parathyroid hormone, and epidermal growth factor on mitogenesis, signaling, and primary response genes in UMR 106-01 osteoblast-like cells

MA Fang, DA Kujubu and TJ Hahn
Geriatric Research, Education, and Clinical Center, Wadsworth Veterans Administration Medical Center, Los Angeles, California 90073.

Prostaglandin E2 (PGE2), PTH, and epidermal growth factor (EGF) are potent regulators of osteoblast proliferation. In UMR 106-01 rat osteosarcoma cells with osteoblast-like features, PGE2 and PTH inhibit, while EGF stimulates, mitogenesis. Both PGE2 and PTH increase intracellular cAMP levels, cytosolic calcium, and inositol phosphate turnover. In a variety of cell types, EGF mediates its effects in part via activation of receptor protein-tyrosine kinase and other protein kinases, such as protein kinase-C. The nuclear mechanisms of PGE2, PTH, and EGF regulation of osteoblast proliferation are unknown. Accordingly, we have examined the effects of these agents on mitogenesis, second messenger generation, and primary response genes, which may link second messenger activation to subsequent alterations in gene expression. Northern blot analysis of mRNA from UMR 106-01 cells treated for 3 h with 2 microM PGE2, 10 nM PTH, or 10 ng/ml EGF in the presence of cycloheximide demonstrated that all three agents induced the expression of c-fos and c-jun mRNA. In contrast, only EGF stimulated cellular proliferation and induced Egr-1 mRNA. Also, unlike PGE2 and PTH, EGF did not increase intracellular cAMP levels. c-fos mRNA was induced by treatment with 50 ng/ml tetradecanoyl phorbol acetate or by 40 ng/ml forskolin, while induction of Egr-1 mRNA was stimulated by treatment with tetradecanoyl phorbol acetate, but not forskolin. Thus, EGF signal transduction differs from that of PGE2 and PTH in UMR 106-01 osteoblast-like cells, in that EGF does not stimulate the protein kinase-A second messenger system, but causes activation of Egr-1, a primary response gene that may play a role in the mitogenic effect of EGF.

This article has been cited by other articles:

				C. J. Xian Roles of Epidermal Growth Factor Family in the Regulation of Postnatal Somatic Growth Endocr. Rev., May 1, 2007; 28(3): 284 - 296. [Abstract] [Full Text] [PDF]

				J. Fitzgerald, T. J. Dietz, and M. Hughes-Fulford Prostaglandin E2-Induced Up-Regulation of c-fos Messenger Ribonucleic Acid Is Primarily Mediated by 3',5'-Cyclic Adenosine Monophosphate in MC3T3-E1 Osteoblasts Endocrinology, January 1, 2000; 141(1): 291 - 298. [Abstract] [Full Text] [PDF]

				S. E. Hahn, M. Yu, S. Tong, A. A.T. Geisterfer-Lowrance, D. Sindrey, and D. K.H. Lee Development of an In Vitro Screening Assay for Compounds that Increase Bone Formation J Biomol Screen, December 1, 1999; 4(6): 363 - 371. [Abstract] [PDF]

				W. Qu, L. M. Graves, and R. G. Thurman PGE2 stimulates O2 uptake in hepatic parenchymal cells: involvement of the cAMP-dependent protein kinase Am J Physiol Gastrointest Liver Physiol, November 1, 1999; 277(5): G1048 - G1054. [Abstract] [Full Text] [PDF]

				T. Onishi and K. Hruska Expression of p27Kip1 in Osteoblast-Like Cells during Differentiation with Parathyroid Hormone Endocrinology, May 1, 1997; 138(5): 1995 - 2004. [Abstract] [Full Text] [PDF]