| Project/Area Number |
09671060
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kobe University |
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Principal Investigator |
SUGIMOTO Toshitsugu Kobe University, Department of Medicine, Assistant, 医学部, 助手 (00226458)
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| Co-Investigator(Kenkyū-buntansha) |
CHIHARA Kazuo Kobe University, Department of Medicine, Professor, 医学部, 教授 (00107955)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Parathyroid hormone / Estrogen / Insulin-like growth factor-l / Insulin-like growth factor-binding protein-5 / Bone formation / Bone resorption / cAMP-dependent protein kinase / Postmenopausal osteoporosis / インスリン様成長因子結合タンパク / cAMP依存性プロテインキナーゼ |
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| Research Abstract |
It is well known that parathyroid hormone (PTH) possesses catabolic as well as anabolic action in bone, but the mechanisms of its anabolic action remained unknown. The present study demonstrated that not only insulin-like growth factor (IGF)-I but also IGF-binding protein-5 (IGFBP-5) were involved in the anabolic action of PTH in bone. Although it has been generally accepted that the biological activity of the PTH molecule mainly exists in the amino-terminal region of this molecule, there have also been several lines of evidence that some biological activities exist in carboxyl-terminal fragment. The present study demonstrated that carboxyl-terminal portion of the PTH molecule exercised biological activities in mRNA expression of type-I procollagen as well as IGFBP-5 in osteoblasts and that these would be involved in the anabolic action of PTH in bone in vivo. Moreover, clinical studies obtained from changes in bone mass after parathyroidectomy in primary hyperparathyroidism demonstrat
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ed that rapid reduction in endogenous PTH concentration played a crucial role in the anabolic action of PTH in bone. On the other hand, several lines of evidence indicate that estrogen inhibits PTH-induced bone resorption in viva and invitro, but its precise mechanisms remained unclear. Our previous study demonstated estrogen inhibited PTH-induced osteoclast formation in unfractionated bone cells, but it remained still unclear what kind of cells in bone were responsible for this interaction between PTH and estrogen. The present study demonstrated that PTH receptors and estrogen receptors both existed in hemopoietic blast cells, that is, osteoclast precursor cells. Estrogen inhibited PTH- induced osteoclast formation by directly acting on hemopoietic blast cells and the inhibitory effects of estrogen on PTH-induced osteoclast formation were mediated through blocking cAMP-dependent protein kinase. The present study indicated that the enhanced PTH-induced osteoclastgenesis in the absence of estrogen was partly involved in the increase in osteoclast number associated with postmenopausal osteoporosis. Less
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