title: Combined effects of caffeine and prostaglandin E2 on the proliferation of osteoblast-like cells (UMR106-01).
abstract: BACKGROUND
  The general public widely consumes caffeine (1,3,7-trimethylxanthine), which is contained in various foods, beverages and over-the-counter medications. We have shown previously that caffeine intake could affect bone metabolism in vivo.
  
  
  METHODS
  Because prostaglandin E2 (PGE2) is shown to be elevated in the periodontally diseased site, the possible interaction between caffeine and PGE2 was investigated in the present study using UMR106-01 rat osteoblast-like cells in vitro.
  
  
  RESULTS
  Although neither 0.1 mM caffeine nor 0.1 microg/ml of PGE2 alone showed any inhibitory effects on cell proliferation, the combination of caffeine and PGE2 showed significant inhibition. However, in order to have inhibitory effects, both caffeine and PGE2 had to be present at least 72 or 96 hours in the medium. Addition of the endogenous PGE2 synthesis inhibitor, indomethacin, showed no effects on cell proliferation. Neither cAMP-inducing agent IBMX (0.01 mM and 0.1 mM) nor forskolin (0.001 mM) inhibited cell proliferation, but combined with PGE2 these agents strongly inhibited proliferation as was observed with the combination of caffeine and PGE2, suggesting possibly that the increase of intracellular cAMP concentration plays an important role in the inhibitory effects of cell proliferation.
  
  
  CONCLUSIONS
  The present data for the first time demonstrate the possible implication of routine caffeine intake in the acceleration of pathological conditions of periodontitis. Thus, we propose that chronic caffeine intake is one of the possible risk factors in the advancement of pathology in the periodontitis patient. Further research in this area is warranted.
authors.affiliation: Department of Physiology, Louisiana State University Medical Center, New Orleans, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kamagata-Kiyoura
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: G
authors.initials: G
authors.lastname: Cheuk
authors.forename: M
authors.initials: M
authors.lastname: Yazdani
authors.forename: M J
authors.initials: MJ
authors.lastname: Saltzman
authors.forename: T
authors.initials: T
authors.lastname: Nakamoto
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007213:Indomethacin / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects*; D010518:Periodontitis / Q000378:metabolism / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D012307:Risk Factors; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D002110:Caffeine; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin