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

• Project/Area Number: 10672112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Teikyo University
• Principal Investigator: KAWASHIMA Kohtaro Teikyo Univ., Pharm. Sci., Professor, 薬学部, 教授 (20124993)
• Co-Investigator(Kenkyū-buntansha): NEGISHI Yoichi Teikyo Univ., Pharm. Sci., Assistant, 薬学部, 助手 (50286978)
• Project Period (FY): 1998 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥3,100,000 (Direct Cost: ¥3,100,000); Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: mechanical stress / hypergravity / osteoblasts / bone-forming agents / alkaline phosphatase / MAP kinase / osteocalcin

Research Abstract

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 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.