Endocrinology, Vol 133, 1504-1510, Copyright © 1993 by Endocrine Society

ARTICLES

Effects of prostaglandin E2 on bone formation in cultured fetal rat calvariae: role of insulin-like growth factor-I

LG Raisz, PM Fall, BY Gabbitas, TL McCarthy, BE Kream and E Canalis
University of Connecticut Health Center, Farmington 06030.

Prostaglandin E2 (PGE2) can stimulate collagen synthesis in bone at low concentrations or in the presence of cortisol. Moreover, cortisol inhibits and PGE2 stimulates the production of insulin-like growth factor (IGF-I) in cultured osteoblastic cells. Therefore, we examined the role of IGF-I in the response to PGE2. In 96-h fetal rat calvarial organ cultures, PGE2 increased, and cortisol and indomethacin decreased the medium IGF-I concentration, suggesting that both exogenous and endogenous PGs regulate IGF-I production. In the presence of cortisol, the stimulatory effects of PGE2 on medium IGF-I and incorporation of [3H] proline into collagenase-digestible protein were highly correlated (r = 0.95). When exogenous IGF-I (30 nM) was added, the stimulatory effect of PGE2 was abrogated in the absence, but not the presence, of cortisol. When we added IGF-binding proteins, which blocked the effects of IGF-I and IGF-II, collagenase-digestible protein labeling was decreased in control and cortisol-treated cultures, whereas the stimulatory effect of PGE2 was reduced, but not abrogated. We conclude that endogenous IGFs play a role in maintaining bone formation in cultured fetal rat calvariae and may mediate in part the anabolic response to PGE2. However, the PGE2 response probably involves additional IGF-independent pathways.

This article has been cited by other articles:

				S C Mastbergen, J W J Bijlsma, and F P J G Lafeber Synthesis and release of human cartilage matrix proteoglycans are differently regulated by nitric oxide and prostaglandin-E2 Ann Rheum Dis, January 1, 2008; 67(1): 52 - 58. [Abstract] [Full Text] [PDF]

				L. G. Raisz Selective Prostaglandin Agonists as Anabolic Agents IBMS BoneKEy, July 1, 2006; 3(7): 15 - 20. [Abstract] [Full Text] [PDF]

				R. C. Mollard, H. R. Kovacs, S. C. Fitzpatrick-Wong, and H. A. Weiler Low Levels of Dietary Arachidonic and Docosahexaenoic Acids Improve Bone Mass in Neonatal Piglets, but Higher Levels Provide No Benefit J. Nutr., March 1, 2005; 135(3): 505 - 512. [Abstract] [Full Text] [PDF]

				P. P. Cherian, B. Cheng, S. Gu, E. Sprague, L. F. Bonewald, and J. X. Jiang Effects of Mechanical Strain on the Function of Gap Junctions in Osteocytes Are Mediated through the Prostaglandin EP2 Receptor J. Biol. Chem., October 31, 2003; 278(44): 43146 - 43156. [Abstract] [Full Text] [PDF]

				B. Cheng, Y. Kato, S. Zhao, J. Luo, E. Sprague, L. F. Bonewald, and J. X. Jiang PGE2 Is Essential for Gap Junction-Mediated Intercellular Communication between Osteocyte-Like MLO-Y4 Cells in Response to Mechanical Strain Endocrinology, August 1, 2001; 142(8): 3464 - 3473. [Abstract] [Full Text] [PDF]

				T. L. McCarthy, C. Ji, Y. Chen, K. Kim, and M. Centrella Time- and Dose-Related Interactions between Glucocorticoid and Cyclic Adenosine 3',5'-Monophosphate on CCAAT/Enhancer-Binding Protein-Dependent Insulin-Like Growth Factor I Expression by Osteoblasts Endocrinology, January 1, 2000; 141(1): 127 - 137. [Abstract] [Full Text] [PDF]

				F. Gori, L. C. Hofbauer, C. A. Conover, and S. Khosla Effects of Androgens on the Insulin-Like Growth Factor System in an Androgen-Responsive Human Osteoblastic Cell Line Endocrinology, December 1, 1999; 140(12): 5579 - 5586. [Abstract] [Full Text]

				R. Patel, M. G. Attur, M. Dave, S. B. Abramson, and A. R. Amin Regulation of Cytosolic COX-2 and Prostaglandin E2 Production by Nitric Oxide in Activated Murine Macrophages J. Immunol., April 1, 1999; 162(7): 4191 - 4197. [Abstract] [Full Text] [PDF]

				M. G. Sabbieti, L. Marchetti, C. Abreu, A. Montero, A. R. Hand, L. G. Raisz, and M. M. Hurley Prostaglandins Regulate the Expression of Fibroblast Growth Factor-2 in Bone Endocrinology, January 1, 1999; 140(1): 434 - 444. [Abstract] [Full Text]

				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]

				C. M. Veldman, I. Schlapfer, and C. Schmid Prostaglandin E2 Stimulates Sodium-Dependent Phosphate Transport in Osteoblastic Cells via a Protein Kinase C-Mediated Pathway Endocrinology, January 1, 1998; 139(1): 89 - 94. [Abstract] [Full Text] [PDF]

				S. Tetradis, C. C. Pilbeam, Y. Liu, H. R. Herschman, and B. E. Kream Parathyroid Hormone Increases Prostaglandin G/H Synthase-2 Transcription by a Cyclic Adenosine 3',5'-Monophosphate-Mediated Pathway in Murine Osteoblastic MC3T3-E1 Cells Endocrinology, September 1, 1997; 138(9): 3594 - 3600. [Abstract] [Full Text] [PDF]

				B. Gabbitas, J. M. Pash, A. M. Delany, and E. Canalis Cortisol Inhibits the Synthesis of Insulin-like Growth Factor-binding Protein-5 in Bone Cell Cultures by Transcriptional Mechanisms J. Biol. Chem., April 12, 1996; 271(15): 9033 - 9038. [Abstract] [Full Text] [PDF]