1995 Fiscal Year Final Research Report Summary
Molecular mechanisms of osteoporosis induced by estrogen deficiency.
| Project/Area Number |
06404067
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
SUDA Tatsuo Showa University, School of Dentistry, Professor, 歯学部, 教授 (90014034)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Takenobu Showa University, School of Dentistry, Assistant, 歯学部, 助手 (80245802)
TAKAHASHI Naoyuki Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (90119222)
MIYAURA Chisato Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (20138382)
SHINKI Toshimasa Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (90138420)
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| Project Period (FY) |
1994 – 1995
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| Keywords | estrogen / androgen / bone resorption / interleukin-1 / interleukin-6 / osteoporosis / hemopoiesis / bone marrow |
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| Research Abstract |
1.Endogenous bone-resorbing factors in estrogen deficiency
Estrogen deficiency causes a marked bone loss by stimulating osteoclastic bone resorption. In this study, we examined the bone-resorbing activity present in the supernatant fraction of mouse bone marrow collected from ovariectomized (OVX) mice. Adding bone marrow supernatants at 20-80% to organ cultures of mouse long bones dose-dependently stimulated bone resorption. Anti-IL-lalpha antibody completely neutralized the bone-resorbing activity present in bone marrow supernatants from OVX mice. Antibodies against IL-lbeta, IL-6 and IL-6 receptors also neutralized it, but partially. The concurrent addition of IL-1, IL-6 and soluble IL-6 receptor, which equaled the endogenous concentrations on bone marrow supernatants from OVX mice, co-operatively induced bone resorption. These results suggest that the enhanced bone resorption that occurs during estrogen deficiency is due to multi-factors rather than to a single factor.
Increased hemopoiesis in sex steroid deficiency.
Estrogen deficiency caused by OVX selectively stimulates B lymphopoiesis, resulting in a marked accumulation of pre-B cells in mouse bone marrow. We compared the effects of estrogen and androgen on B lymphopoiesis in bone marrow and bone metabolism using orchidectomised (ORX) mice. Some of the ORX mice were treated with estrogen or androgen. At3 weeks after operation, in ORX mice, the number of bone marrow cells were markedly increased, and most of the increased cells were B220-positive pre-B lymphocytes. The characteristics of the accumulated cells and the time course of changes of the stimulated B lymphopoiesis after operation were quite similar to those in OVX mice. These changes of hemopoiesis and bone metabolism induced by ORX were completely restored by the treatment of estrogen. These results suggest that estrogen regulates B lymphopoiesis and bone metabolism not only in female but also in male mice.
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