University of Science and Technology of China, Hefei, China.
Cell Biochem Funct. 2010 Jun;28(4):334-41. doi: 10.1002/cbf.1668.
Insulin has been proposed to be an anabolic agent in bone, but the mechanisms underlying insulin effects on osteoblast differentiation are still not clear. To explore the mechanisms of action of insulin on osteoblast growth and differentiation, human osteoblastic cell line-MG-63 was used and stimulated by insulin in the presence or absence of ERK inhibitor PD98059, PI3-K inhibitor LY294002, or inhibitor PD98059 + LY294002. The results showed that insulin positively regulated the expression of its receptor. Insulin stimulated the proliferation of MG-63 cells in a time- and dose-dependent manner and blockade of both MAPK and PI3K pathways could inhibit the cell proliferation. In addition, ALP activity, the secretion of type I collagen, OC gene expression, and mineralized nodule formation were increased in the insulin treated group, whereas these indicators were decreased after treatment with blocking agents. However, treatment with PI3-K inhibitor LY294002 significantly reversed the down-regulation of Runx2 expression and treatment with ERK inhibitor PD98059 remarkably decreased up-regulation of Osx and IGF-1 expression after insulin treatment. Therefore, the data obtained from this study suggested that insulin promoted osteoblast proliferation and differentiation through MAPK and PI3K pathway in MG-63 cells.
胰岛素被认为是骨骼中的一种合成代谢剂，但胰岛素对成骨细胞分化的作用机制尚不清楚。为了探讨胰岛素对成骨细胞生长和分化的作用机制，我们使用人成骨样细胞株 MG-63，并在存在或不存在 ERK 抑制剂 PD98059、PI3-K 抑制剂 LY294002 或抑制剂 PD98059+LY294002 的情况下用胰岛素刺激该细胞。结果表明，胰岛素正向调节其受体的表达。胰岛素以时间和剂量依赖的方式刺激 MG-63 细胞的增殖，而 MAPK 和 PI3K 通路的阻断均可抑制细胞增殖。此外，胰岛素处理组的 ALP 活性、I 型胶原分泌、OC 基因表达和矿化结节形成增加，而阻断剂处理后这些指标降低。然而，用 PI3-K 抑制剂 LY294002 处理可显著逆转胰岛素处理后 Runx2 表达的下调，而用 ERK 抑制剂 PD98059 处理则可显著降低胰岛素处理后 Osx 和 IGF-1 表达的上调。因此，本研究结果表明，胰岛素通过 MAPK 和 PI3K 通路促进 MG-63 细胞中的成骨细胞增殖和分化。
