Kanatani M, Sugimoto T, Fukase M, Chihara K
Department of Medicine, Kobe University School of Medicine, Japan.
Biochem Biophys Res Commun. 1993 Jan 29;190(2):529-35. doi: 10.1006/bbrc.1993.1080.
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.
一些证据表明，单核细胞在骨重塑部位的骨吸收与骨形成偶联过程中发挥着重要作用。因此，我们研究了用1,25 - 二羟基维生素D3 [1,25(OH)2D3]处理的人单核细胞条件培养基（CM）对成骨MC3T3 - E1细胞增殖的影响。1,25(OH)2D3（10^(-11) - 10^(-8)）以剂量相关的方式直接抑制[3H]胸腺嘧啶核苷掺入（TdR）到MC3T3 - E1细胞中。与1,25(OH)2D3相比，24,25(OH)2D3和25(OH)D3（10^(-8)和10^(-7) M）仅具有适度的抑制作用。另一方面，CM本身显著刺激TdR，而从用1,25(OH)2D3（10^(-10)和10^(-8) M）处理的单核细胞获得的CM则显著抑制TdR。与10^(-8) M 1,25(OH)2D3相比，用10^(-7) M 25(OH)D3处理单核细胞在较小程度上显著抑制CM诱导的TdR刺激，而用10^(-7) M 24,25(OH)2D3处理单核细胞不影响CM诱导的TdR刺激。1,25(OH)2D3处理的CM对TdR的抑制作用被前列腺素合成抑制剂10^(-6) M消炎痛显著阻断。目前的数据首先表明，1,25(OH)2D3不仅直接抑制成骨细胞增殖，还通过调节单核细胞释放与骨重塑相关的局部因子间接抑制，并且还表明其通过单核细胞的间接作用至少部分是通过前列腺素合成介导的。
