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

超重力和成骨剂对成骨细胞代谢的协同作用

• 批准号: 10672112
• 负责人: KAWASHIMA Kohtaro
• 金额: $ 1.98万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672112/
• 关键词: mechanical stress; hypergravity; osteoblasts; bone-forming agents; alkaline phosphatase; MAP kinase; osteocalcin

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

在这个项目中，我们研究了成骨药物和机械应力对成骨细胞不同功能的协同作用。我们使用超重力作为机械应力，因为我们之前表明，成骨细胞样ROS17/2.8细胞暴露于超重力会刺激碱性磷酸酶活性、骨钙素合成和胶原蛋白合成等分化功能。 ROS17/2.8细胞暴露于超重力会增加活性维生素D3刺激的骨钙素合成、香豆雌酚衍生物(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，表明超重力对刺激由成骨剂诱导的分化功能具有累加效应。这些结果表明机械应力和骨形成剂的同时治疗可能会改善骨质疏松症。我们之前表明，超重力的加载会重新排列细胞骨架。研究表明，丝裂原激活蛋白激酶（MAP 激酶）对细胞分化具有重要作用，并且与细胞骨架有关。因此，为了研究超重力的作用机制，我们接下来检查了超重力对成骨细胞MAP激酶活性的影响。 PD098059 是一种 MAP 激酶抑制剂，对对照细胞和超重力 ROS17/2.8 细胞的细胞生长都有抑制作用，表明 PD098059 抑制 MAP 激酶活性。然而，PD098059 增加了对照细胞和超重力 ROS17/2.8 细胞的碱性磷酸酶活性。这些结果表明，MAP激酶通常抑制对照细胞中的碱性磷酸酶活性，超重力的加载导致MAP激酶的抑制，导致碱性磷酸酶活性的激活。为了估计成骨剂和超重力的协同作用，我们现在正在研究成骨剂对 MAP 激酶活性的影响。较少的