RT Journal Article
SR Electronic
T1 Prostaglandin production by human osteoclasts in culture.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1320
OP 1328
VO 33
IS 7
A1 Josette A Hackett
A1 Hugues Allard-Chamard
A1 Patrice Sarrazin
A1 Maria de Fatima Lucena
A1 Maxime A Gallant
A1 Isabelle Fortier
A1 Moni Nader
A1 Jean-Luc Parent
A1 Ghassan Bkaily
A1 Artur J de Brum-Fernandes
YR 2006
UL http://www.jrheum.org/content/33/7/1320.abstract
AB 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.