Induction of cyclooxygenase-2 by parathyroid hormone in human osteoblasts in culture.
OBJECTIVE
Parathyroid hormone (PTH) induced bone resorption by osteoclasts depends on the presence of osteoblasts. PTH induced production of prostaglandins by osteoblasts and induction of bone resorption by prostaglandins suggest that these autacoids may be implicated in the effects of PTH on bone. Our objective was to determine if the increase in prostaglandin production induced in human osteoblasts by PTH is due to an increase in cyclooxygenase-2 (COX-2) expression.


METHODS
Primary cultures of human osteoblasts were obtained from specimens of trabecular bone. Confluent cells were treated with PTH, dexamethasone or compound NS-398, a specific COX-2 inhibitor. The concentration of prostaglandin E2 (PGE2) in the supernatants was determined by radioimmunoassay and COX-2 mRNA levels evaluated by Northern blot.


RESULTS
PTH induced COX-2 mRNA expression and PGE2 production. These effects were time and concentration dependent and were inhibited by dexamethasone. Compound NS-398 reduced PGE2 production to the same extent as dexamethasone, and neither compound had an additive effect on this variable.


CONCLUSIONS
These results show that PTH induces COX-2 expression in human osteoblasts in culture and suggest that this isoenzyme is the main factor in the control of prostaglandin synthesis in these experimental conditions.
Maciel
F M
FM
Department of Medicine, Faculté de Médicine, Université de Sherbrooke, Canada.
Sarrazin
P
P
Morisset
S
S
Lora
M
M
Patry
C
C
Dumais
R
R
de Brum-Fernandes
A J
AJ
D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone