Mitogenic action of adenosine on osteoblast-like cells, MC3T3-E1.
The purpose of this study was to investigate the mechanisms by which adenosine stimulates proliferation of osteoblast-like cells, MC3T3-E1. Adenosine by itself induces the stimulation of cell proliferation and accentuates the mitogenecity of PDGFs (AA and BB homodimers) for the cells. 8-Cyclopentyl-1,3-dimethylxanthine (CPX), a nonselective adenosine receptor antagonist, partially inhibited adenosine-induced DNA synthesis in a competitive manner, suggesting that the mitogenic action of adenosine is, at least in part, mediated by xanthine-sensitive receptors. In pertussis-toxin (PTX)-pretreated cells, adenosine- but not PDGF-BB-stimulated DNA synthesis was partially inhibited, and CPX did not exert a further inhibitory effect, suggesting an involvement of PTX-sensitive G-protein downstream of CPX-sensitive receptor. When adenosine uptake was prevented with dipyridamole, the stimulation of proliferation by adenosine was not decreased at all, indicating that the CPX-insensitive part of adenosine action is not associated with the uptake of adenosine and subsequent incorporation into the nucleotide pool. Adenosine did not influence the basal level or the PDGF-BB-induced increase in [Ca2+]i. Since it is known that the cAMP pathway acts in inhibiting osteoblast proliferation, the mitogenic action of adenosine would be dependent on neither the cAMP pathway nor the phospholipase C/Ca2+ pathway. It has been concluded that adenosine exerts a mitogenic effect via two pathways at least, one mediated by xanthine-sensitive receptor and PTX-sensitive G-protein and the other through an unknown xanthine- and PTX-insensitive process.
Shimegi
S
S
Faculty of Health and Sport Sciences, Osaka University, Toyonaka, Osaka 560, Japan.
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004176:Dipyridamole / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D058915:Purinergic P1 Receptor Antagonists; D010566:Virulence Factors, Bordetella; C075278:platelet-derived growth factor A; D000077214:Becaplermin; C053907:8-cyclopentyl-1,3-dimethylxanthine; D004176:Dipyridamole; D004247:DNA; D013806:Theophylline; D037342:Pertussis Toxin; D000241:Adenosine; D002118:Calcium; D013936:Thymidine