ATP AND ADENOSINE ACT AS A MITOGEN FOR OSTEOBLAST-LIKE CELLS (MC3T3-E1)

Extracellular ATP, and to a lesser extent adenosine, an ATP metabolite , stimulated cell proliferation in osteoblast-like cells (MC3T3-E1). A TP increased cytosolic Ca2+ due to Ca2+ mobilization from intracellula r storage in the same concentration range of the nucleotide as that ef fective for DNA synthesis, suggesting the mediation of the phospholipa se C/Ca2+ system in the mitogenic action. Since adenosine induced no C a2+ mobilization, P-2-purinergic receptor appears to be associated wit h ATP actions. The growth-promoting effect nf ATP was not inhibited by H7, a protein kinase C inhibitor, and indomethacin, a cyclooxygenase inhibitor, indicating no involvement of activation of protein kinase C and production of prostaglandins in ATP-induced mitogenic signals. Ei ther ATP or adenosine remarkably and synergistically potentiated plate let derived growth factor-induced DNA synthesis. These findings sugges t that extracellular ATP and adenosine may play a physiological role i n the regulation of bone formation.