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Prostaglandin Production by Human Osteoclasts in Culture
JOSETTE A. HACKETT, HUGUES ALLARD-CHAMARD, PATRICE SARRAZIN, MARIA de FATIMA LUCENA, MAXIME A. GALLANT, ISABELLE FORTIER, MONI NADER, JEAN-LUC PARENT, GHASSAN BKAILY, and ARTUR J. de BRUM-FERNANDES ABSTRACT.
Objective. Prostaglandins (PG) are important mediators of bone metabolism with direct and indirect effects on bone cells. They may have important effects on osteoclasts, but it is not known if these cells can synthesize PG. We used 2 experimental models in order (1) to determine the presence and functionality of cyclooxygenase (COX) and phospholipase A2 (PLA2) enzymes in human osteoclasts and (2) to study their role in cell metabolism.
Methods. Experiments were undertaken on authentic human osteoclasts extracted from human fetuses (fhOC) and on human osteoclast-like (hOCL) cells differentiated from peripheral blood mononuclear cells. The presence of COX proteins was determined by immunohistochemistry. COX and PLA2 enzymatic activity was evaluated at the single-cell level by fluorescence microscopy. An enriched population of hOCL cells was used to evaluate total PG production and the influence of COX activity on bone resorption. Results. COX-1 was expressed in the cytoplasm and COX-2 was distributed mainly near the nuclear membrane of osteoclasts. These cells showed a high basal level of COX activity that could be inhibited by pretreatment with COX inhibitors. Cytosolic PLA2 was present in both models. Human osteoclasts actively produced PG, and the COX-1 pathway was implicated in the control of bone resorption. Conclusion. These results indicate that PG may be important autacoids for the control of osteoclast biology and that the COX-1 pathway is implicated in the inhibition of bone resorption. (First Release June 1 2006; J Rheumatol 2006;33:1320–8) Key Indexing Terms:
CYCLOOXYGENASES
From the Division of Rheumatology and the Department of Anatomy and Cellular Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada. Supported by grants from The Arthritis Society, the Canadian Institutes for Health Research, and the Fonds de la recherché en santé du Québec. J.A. Hackett, MSc; H. Allard-Chamard, BSc; P. Sarrazin, PhD; M.F. Lucena, MD, MSc; M. Gallant, MSc; I. Fortier, MSc, DVM; J-L. Parent, PhD, Professor; A.J. de Brum-Fernandes, MD, PhD, Professor, Division of Rheumatology, Faculty of Medicine; M. Nader, PhD; G. Bkaily, PhD, Professor, Department of Anatomy and Cellular Biology, Faculty of Medicine, Université de Sherbrooke. Address reprint requests to Dr. A.J. de Brum-Fernandes, Division of Rheumatology, Centre de Recherche Clinique, Centre Hospitalier Universitaire de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, Québec J1H 5N4, Canada. E-mail: Artur.Fernandes@USherbrooke.ca Accepted for publication February 26, 2006.
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