Chloride-dependent acceleration of cell cycle via modulation of Rb and cdc2 in osteoblastic cells

In the present study, we investigated if Cl− regulates the proliferation of the MC3T3-E1 osteoblastic cells. The proliferation of MC3T3-E1 osteoblastic cells was diminished by lowering the extracellular Cl− concentration ([Cl−]o) in the culture medium. The lowered in [Cl−]o increased the periods of the G0/G1 and the G2/M phases in cell cycle. We further studied the effects of [Cl−]o on the key enzymes, Rb and cdc2, playing key roles in checking points of the G0/G1 and the G2/M phases in cell cycle. The lowered in [Cl−]o diminished the active forms of enzymes, Rb and cdc2. We further found that the action of lowered [Cl−]o on the cell proliferation, the cell cycle, Rb and cdc2 was abolished by the presence of 2 mM glutamine, but not by that of pyruvate as another Krebs cycle substrate. Taken together, these observations indicate here for the first time that Cl− modulates Rb and cdc2, enhancing the proliferation of the MC3T3-E1 osteoblastic cells.