Effect of 1,25-dihydroxyvitamin D3 on the proliferation of osteoblastic MC3T3-E1 cells by modulating the release of local regulators from monocytes.

Some evidence suggests an important role of mononuclear cells at the bone remodeling sites in the coupling of bone resorption to bone formation. Therefore, we examined effects of human monocytes-conditioned medium (CM) treated with 1,25-dihydroxyvitamin D3 [1.25(OH)2D3] on the proliferation of osteoblastic MC3T3-E1 cells. 1,25(OH)2D3 (10(-11)-10(-8) directly inhibited [3H]thymidine incorporation (TdR) into MC3T3-E1 cells in a dose-related fashion. 24,25(OH)2D3 and 25(OH)D3 (10(-8) and 10(-7) M) had only modest inhibitory effect, compared to that of 1,25(OH)2D3. CM, per se, on the other hand, significantly stimulated TdR, whereas CM obtained from monocytes treated with 1,25(OH)2D3(10(-10) and 10(-8) M) significantly inhibited TdR. Treatment of monocytes with 10(-7) M 25(OH)D3 significantly inhibited CM-induced stimulation of TdR to a lesser degree, compared to that of 10(-8) M 1,25(OH)2D3 and treatment of monocytes with 10(-7) M 24,25(OH)2D3 did not affect CM-induced stimulation of TdR. The inhibition of TdR by 1,25(OH)2D3-treated CM was significantly blocked by 10(-6) M indomethacin, an inhibitor of prostaglandin synthesis. Present data first indicate that 1,25(OH)2D3 inhibited osteoblast proliferation not only directly but also indirectly through modulating the release of local factors as to bone remodeling from monocytes, and also suggest that its indirect effect via monocytes was mediated at least in part through prostaglandin synthesis.