Involvement of prostaglandin endoperoxide H synthase-2 in osteoclast formation induced by parathyroid hormone.
Prostaglandin (PG)E2 is one of the most important endogenous bone resorbing factors. In the previous study, we demonstrated that osteoclast formation induced by IL-1 beta was mediated by PGE2 produced by induced prostaglandin endoperoxide H synthase-2 (PGHS-2) in osteoclastic cells. In the same bone marrow culture system, indomethacin also suppressed the osteoclast formation induced by PTH. The inhibition was abolished by exogenously added PGE2 at dose as low as 3 x 10(-9) M, which was too low to elevate the intracellular cAMP and calcium levels and also it was too low to cause osteoclast formation by itself. In order to estimate what kind of cell produced such small amount of PGE2 in the PTH treatment, we carried out antibody staining of PGHS-1&PGHS-2 and PGHS activity in the intact bone marrow cells. PTH was found to induce PGHS activity in tartrate-resistant acid phosphatase (TRACP) positive mononuclear cells and the PGHS activity was inhibited by NS-398, a specific inhibitor of PGHS-2. Immunocytochemical staining supported the expression of PGHS-2 in TRACP-positive mononuclear cells. These findings suggest that PGHS-2 induced by PTH may regulate osteoclast formation by different mechanism from that induced by IL-1 beta.
Tokushima
T
T
Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental Univeristy, Japan.
Sato
T
T
Morita
I
I
Murota
S
S
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D015232:Dinoprostone; D007213:Indomethacin