Document Detail

Cyclooxygenase inhibitors enhance cell growth in an osteoblastic cell line, MC3T3-E1.
MedLine Citation:
PMID:  2510469     Owner:  NLM     Status:  MEDLINE    
To elucidate the significance of endogenous prostaglandin E2 (PGE2) in osteoblastic cell function, we studied the effects of cyclooxygenase inhibitors on cell growth and alkaline phosphatase (ALP) activity in MC3T3-E1 cells. UMR-106 cells were also used as references in our experiments. MC3T3-E1 cells, cultured in alpha-minimal essential medium containing 10% fetal bovine serum, were shown to produce PGE2, which was markedly suppressed in the presence of indomethacin. Addition of indomethacin resulted in an increase in DNA content and [3H]thymidine incorporation. A similar growth stimulatory effect was observed when structurally different cyclooxygenase inhibitors, that is, acetyl salicylic acid (ASA), flurbiprofen, and piroxicam, were added. These cyclooxygenase inhibitors, however, differed in their effects on ALP activity. Indomethacin and ASA enhanced ALP activity, whereas flurbiprofen and piroxicam suppressed it. We then examined the effects of exogenous addition of PGE2. Although exogenous PGE2 at 6 x 10(-6) M slightly stimulated cell growth, it inhibited cell growth at 6 x 10(-8) M and 6 x 10(-7) M. ALP activity was reduced in a dose-dependent fashion by exogenous PGE2. These results suggest that PGE2 produced by MC3T3-E1 may be suppressing cell proliferation and that cyclooxygenase inhibitors, per se, may stimulate cell growth by inhibiting endogenous PGE2 production in MC3T3-E1 cells. UMR-106 cells also produced PGE2, although less than MC3T3-E1 cells. In UMR-106 cells, the cyclooxygenase inhibitors did not influence DNA content or ALP activity as distinctly as in MC3T3-E1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
A Fujimori; M Tsutsumi; M Fukase; T Fujita
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  4     ISSN:  0884-0431     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  1989 Oct 
Date Detail:
Created Date:  1989-12-08     Completed Date:  1989-12-08     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  697-704     Citation Subset:  IM    
Department of Medicine, Kobe University School of Medicine.
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MeSH Terms
Alkaline Phosphatase / metabolism
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Cell Division / drug effects
Cell Line
Cyclooxygenase Inhibitors
DNA / analysis,  biosynthesis
Dinoprostone / metabolism
Osteoblasts / cytology,  drug effects*
Thymidine / metabolism
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cyclooxygenase Inhibitors; 363-24-6/Dinoprostone; 50-89-5/Thymidine; 9007-49-2/DNA; EC Phosphatase

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