MITOGENIC ACTION OF ADENOSINE ON OSTEOBLAST-LIKE CELLS, MC3T3-E1

The purpose of this study was to investigate the mechanisms by which a denosine stimulates proliferation of osteoblast-like cells, MC3T3-E1. Adenosine by itself induces the stimulation of cell proliferation and accentuates the mitogenicity of PDGFs (AA and BB homodimers) for the c ells. 8-Cyclopentyl-1,3-dimethylxanthine (CPX), a nonselective adenosi ne receptor antagonist, partially inhibited adenosine-induced DNA synt hesis in a competitive manner, suggesting that the mitogenic action of adenosine is, at least in part, mediated by xanthine-sensitive recept ors. 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-se nsitive G-protein downstream of CPX-sensitive receptor. When adenosine uptake was prevented with dipyridamole, the stimulation of proliferat ion by adenosine was not decreased at all, indicating that the CPX-ins ensitive part of adenosine action is not associated with the uptake of adenosine and subsequent incorporation into the nucleotide pool. Aden osine did not influence the basal level or the PDGF-BB-induced increas e in [Ca2+]i. Since it is known that the cAMP pathway acts in inhibiti ng osteoblast proliferation, the mitogenic action of adenosine would b e dependent on neither the cAMP pathway nor the phospholipase C/Ca2+ p athway. It has been concluded that adenosine exerts a mitogenic effect via two pathways at least, one mediated by xanthine-sensitive recepto r and PTX-sensitive G-protein and the other through an unknown xanthin e- and PTX-insensitive process.