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Implication of Prostaglandin Receptors in the Accumulation of Osteoprotegerin in Human
Osteoblast Cultures
RANA SAMADFAM, MAXIME A. GALLANT, MARIE-CLAUDE MIOUSSE, JEAN-LUC PARENT, and ARTUR J. de BRUM-FERNANDES ABSTRACT. Objective. Prostaglandins are important mediators in bone metabolism and in pathologies such as rheumatoid arthritis and osteoarthritis. We investigated the roles of cyclooxygenases (COX) and prostaglandin receptors in the accumulation of osteoprotegerin (OPG) in the supernatants of human osteoblasts in culture. Methods. Three different cellular models were used, the human osteosarcoma cell lines MG-63 and Saos-2, and primary cultures of human osteoblasts. OPG concentrations were determined by ELISA. Results. RT-PCR analysis showed that, like primary human osteoblasts, MG-63 cells express DP, EP4, FP, IP, and TP receptors, whereas the Saos-2 cells lack IP. Concentration of OPG was highest in MG-63 cell supernatants (36 ± 12.5 ng/ml), followed by human osteoblasts (12.77 ± 2.2 ng/ml) and Saos-2 (3.6 ± 0.76 ng/ml). COX inhibitors did not alter these values. Prostaglandin E2 and BW 245C (a synthetic DP receptor agonist) decreased OPG in the supernatants of human osteoblasts but not in immortalized cell lines. These effects were concentration-dependent and were inhibited by EP4 and DP receptor antagonists. Fluprostenol, an FP receptor agonist, increased the accumulation of OPG in MG-63 but not in primary human osteoblasts or Saos-2. Conclusion. Our results show that activation of EP4 or DP receptors decreased the accumulation of OPG in supernatants of osteoblasts in culture, and suggest that these receptors could be interesting pharmacological targets in bone diseases. They also demonstrate important differences between primary osteoblasts and immortalized cell lines, both in the distribution and in the effects mediated by prostaglandin receptors. (J Rheumatol 2006;33:1167–75) Key Indexing Terms:
OSTEOPROTEGERIN
From the Division of Rheumatology, Faculty of Medicine, Université de Sherbrooke, Fleurimont, Québec, Canada. Supported by grants to Dr. de Brum-Fernandes from the Canadian Institutes of Health Research, The Arthritis Society, and the Canadian Arthritis Network. M.A. Gallant is supported by doctoral fellowships from the Canadian Arthritis Network and the Fonds de la Recherche en Santé du Québec. R. Samadfam, PhD; M.A. Gallant, MSc; M-C. Miousse, MSc; J-L. Parent, PhD, Associate Professor; A.J. de Brum-Fernandes, MD, PhD, Professor, Division of Rheumatology. Address reprint requests to Dr. A.J. de Brum-Fernandes, Division of Rheumatology, Faculty of Medicine, Université de Sherbrooke, 3001 12th Avenue North, Fleurimont, Québec J1H 5N4, Canada. E-mail: Artur.Fernandes@USherbrooke.ca Accepted for publication January 26, 2006.
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