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Differential Effects of Nonsteroidal Anti‐Inflammatory Drugs on Constitutive and Inducible Prostaglandin G/H Synthase in Cultured Bone Cells
Author(s) -
Pilbeam Carol C.,
Fall Pamela M.,
Alander Cynthia B.,
Raisz Lawrence G.
Publication year - 1997
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1997.12.8.1198
Subject(s) - nabumetone , prostaglandin h2 , flurbiprofen , piroxicam , prostaglandin , cell culture , chemistry , naproxen , metabolite , prostaglandin e2 , pharmacology , bone remodeling , mechanism of action , prostaglandin d2 , bone cell , diclofenac , dinoprostone , endocrinology , cyclooxygenase , enzyme , biochemistry , nonsteroidal , in vitro , biology , medicine , pathology , genetics , alternative medicine
The production of prostaglandins by osteoblasts is an important mechanism for the regulation of bone turnover. Bone cells contain both inducible and constitutive prostaglandin G/H synthase (PGHS‐2 and PGHS‐1) and these are differentially regulated. Nonsteroidal anti‐inflammatory drugs (NSAIDs), which selectively inhibit one of these enzymes, would be useful in assessing their relative roles in bone metabolism. By Northern analysis, only PGHS‐2 is expressed by the immortalized rat osteoblastic cell line, Py1a, while only PGHS‐1 is expressed by the rat osteosarcoma cell line, ROS 17/2.8. We tested the relative inhibitory potency (IC 50 ) of seven different NSAIDs on these two cell lines. A recently described selective inhibitor of PGHS‐2, NS‐398, was approximately 30 times more potent in inhibiting PGHS‐2 than PGHS‐1, and diclofenac was approximately 10 times more potent. Both had IC 50 's of approximately 3 nM for PGHS‐2 in Py1a cells. Indomethacin, flurbiprofen, naproxen, and piroxicam were relatively nonselective with IC 50 's ranging from 30 nM to 1 μM, while 6‐methoxy‐2 naphthyl acetic acid, the active metabolite of nabumetone, was inhibitory only at concentrations greater than 1 μM. These results indicate that the presently available NSAIDs are unlikely to distinguish completely between effects mediated by PGHS‐2 or PGHS‐1. However, the cell systems employed could provide a model for the analysis of new compounds with greater selective activity.