CO-OPERATIVE EFFECTS OF HYPERGRAVITY AND BONE FORMING AGENTS ON THE METABOLISM OF OSTEOBLASTS

在本项目中，我们研究了成骨药物和机械应力对成骨细胞不同相关功能的协同作用。我们使用超重力作为机械应力，因为我们之前的研究表明，成骨样ROS17/2.8细胞暴露在超重力下会刺激分化功能，如碱性磷酸酶活性、骨钙素合成和胶原合成。将ROS17/2.8细胞暴露于超重力下，可增加维生素D3刺激的骨钙素合成、香豆素衍生物(KCA-098)刺激的碱性磷酸酶活性和甲状旁腺激素刺激的cAMP合成，表明超重力对成骨物质诱导的分化功能的刺激具有相加作用。这些结果提示，机械应力和成骨剂的同时治疗可能会带来骨质疏松的改善。我们之前展示了超级…的加载更大的重力使细胞骨架重新排列。提示丝裂原活化蛋白激酶(MAP)在细胞分化过程中起重要作用，并与细胞骨架有关。因此，为了研究超重力的作用机制，我们接下来研究了超重力对成骨细胞MAP激酶活性的影响。MAP激酶抑制剂PD098059对ROS17/2.8细胞生长有抑制作用，显示PD098059抑制MAP激酶活性。然而，PD098059增加了对照组和超重力处理的ROS17/2.8细胞的碱性磷酸酶活性。这些结果表明，MAP普通抑制对照细胞的碱性磷酸酶活性，超重负荷带来MAP的抑制，导致碱性磷酸酶的激活。为了评估骨形成剂和超重力的协同作用，我们现在正在研究骨形成剂对MAP激酶活性的影响。较少

In this project we studied the co-operative effects of the bone-forming drugs and the mechanical stress on the different iated functions of osteoblasts. We used hypergravity as mechanical stress because we previously showed that the exposure of osteoblast-like ROS17/2.8 cells to hypergravity brought the stimulation of differentiated functions such as alkaline phosphatase activity, osteocalcin synthesis, and collagen synthesis. Exposure of ROS17/2.8 cells to hypergravity increased active vitamin D3-stimulated osteocalcin synthesis, coumestrol derivative (KCA-098)-stimulated alkaline phosphatase activity, and parathyroid hormone-stimulated cAMP synthesis, showing that the hypergravity has additive effects on the stimulation of differentiated functions induced by the bone-forming agents. These results suggested the possibility that the simultaneous treatment of mechanical stress and bone-forming agents would bring the improvement of osteoporosis. We showed before that the loading of hyper … More gravity rearranged the cytoskeleton. It is suggested that Mitogen Activated Protein Kinase (MAP kinases) had important roles on cell differentiation and were linked to cytoskeleton. Therefore, to investigate the action mechanism of hypergravity, we next examined the effect of hypergravity on the MAP kinase activity of osteoblasts. PD098059, a MAP kinase inhibitor, brought the inhibition of cell growth of both control and hypergravity-subjected ROS17/2.8 cells, showing that PD098059 inhibited the MAP kinase activity. However, PD098059 increased the alkaline phosphatase activity of both control and hypergravity-subjected ROS17/2.8 cells. These results showed that MAP kinase ordinary inhibited the alkaline phosphatase activity in control cells and the loading of hypergravity brought the inhibition of MAP kinase, resulting the activation of alkaline phosphatase activity. To estimate the co-operative effect of bone-forming agents and hypergravity, we are now investigating the effects of bone-forming agents on the MAP kinase activity. Less