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Pathogenesis of bone loss due to estrogen deficiency : Relationship between increased B-lymphopoiesis and bone resorption.

Research Project

Project/Area Number 08407060
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

SUDA Tatsuo  Showa University, School of Dentistry, Professor, 歯学部, 教授 (90014034)

Co-Investigator(Kenkyū-buntansha) UDAGAWA Nobuyuki  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (70245801)
TAKAHASHI Naoyuki  Showa University, School of Dentistry, Associate Professor, 歯学部, 助教授 (90119222)
JIMI Eijiro  Showa University, School of Dentistry, Assistant, 歯学部, 助手 (40276598)
MIYAURA Chisato  Showa University, School of Dentistry, Lecturer, 歯学部, 講師 (20138382)
片桐 岳信  昭和大学, 歯学部, 助手 (80245802)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥26,700,000 (Direct Cost: ¥26,700,000)
Fiscal Year 1997: ¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 1996: ¥15,900,000 (Direct Cost: ¥15,900,000)
Keywordsosteoporosis / estrogen / bone resorption / hemopoiesis / B cells / interleukin-7 / ovariectomy / bone mineral density / アンドロゲン / 骨髄 / 骨代謝
Research Abstract

Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated osteoclastic bone resorption. Recent studies indicated the possible involvement of bone-resorbing cytokines such as interleukin (lL) -1, IL-6 and tumor necrosis factor alpha in bone loss due to estrogen deficiency.In this study, we found that OVX selectively stimulated B-lymphopoiesis which resulted in a marked accumulation of pre-B cells in mouse bone marrow. Like estrogen deficiency, androgen deficiency also stimulated B-lymphopoiesis in mouse bone marrow prior to bone loss. To examine the possible relationship between stimulated B-lymphopoiesis and bone loss, female mice were treated with IL-7, which stimulates B-lymphopoiesis in bone marrow. The increased B-lymphopoiesis induced by IL-7 resulted in a marked bone loss by stimulating bone resorption in mice with intact ovarian function. The extent of bone loss was similar to that in OVX mice, measured by bone mineral density (BMD) and muCT analysis. A higher bone mass was detected in IL-7 receptor-knockout mice in which B-lymphopoiesis was markedly reduced. The results obtained in this stuby show that the perturbation of B-lymphopoiesis in bone marrow is closely linked to the change in bone mass. Increased B-lymphopoiesis due to sex steroid deficiency may be involved in the mechanism of stimulated bone resorption.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Suda, T., et al.: "Pathogenesis of bone loss due to estrogen deficiency." Osteoporosis Int.7. S43-S46 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda, T., et al.: "Regulation of osteoclast function." J. Bone Miner. Res.12. 869-879 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyaura, C., et al.: "Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function." Proc. Natl. Acad. Sci. USA. 94. 9360-9360 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onoe, Y., et al.: "Expression of estrogen receptor β in rat bone." Endocrinology. 138. 4509-4512 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kotake, S., et al.: "Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation." J. Bone Miner. Res.11. 88-95 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chaki, O., et al.: "Androgen deficiency stimulates B-lymphopoiesis in bone marrow and induces bone loss in male mice : comparison of the effects of estrogen and androgen." Osteoporosis 1996. 37-41 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda, T., et al.: "Vitamin D" Vitamin D and osteoclastogenesis., 20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda, T., et al.: "Principle of Bone Biology" Cells of bone : Osteoclast generation., 25 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda, T.et al.: "Pathogenesis of bone loss due to estrogen deficiency." Osteoporosis lnt.7. S43-S46 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda, T.et al.: "Regulation of osteoclast function." J.Bone Miner.Res.12. 869-879 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyaura, C.et al.: "Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function." Proc.Natl.Acad.Sci.USA. 94. 9360-9365 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onoe, Y.et al.: "Expression of estrogen receptor beta in rat bone" Endocrinology. 138. 4509-4512 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kotake, S.et al.: "Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation." J.Bone Miner.Res.11. 88-95 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chaki, O.et al.: "Androgen deficiency stimulates B-lymphopoiesis in bone marrow and induces bone loss in male mice : Comparison of the effects of estrogen and androgen." Osteoporosis 1996. 37-41 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Jimi, E.et al.: "Interleukin-1alpha activates an NF-kB-like factor in osteoclast-like cells." J.Biol.Chem.271. 4605-4608 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda, T.et al.: "Vitamin D and osteoclastogenesis." Vitamin D. 219-339 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda, T.et al.: "Cells of bone : Osteoclast generation" Principle of Bone Biology. 87-102 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suda,T.,et al.: "Pathogenesis of bone loss due to estrogen deficiency." Osteoporosis Int.7. S43-S46 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suda,T.,et al.: "Regulation of osteoclast function." J.Bone Miner.Res.12. 869-879 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyaura,C.,et al.: "Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function." Proc.Natl.Acad.Sci.USA. 94. 9360-9365 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Onoe,Y.,et al.: "Expression of estrogen receptor β in rat bone." Endocrinology. 138. 4509-4512 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi,N.,et al.: "Lack of vacuolar proton ATPase association with the cytoskeleton in osteoclasts of osteosclerotic (oc/oc) mice." FEBS Lett.401. 207-212 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Udagawa,N.,et al.: "Interleukin-18 (interferon-γ-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-γ to inhibit osteoclast formation." J.Exp.Med.185. 1005-1012 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suda,T.,et al.: "Vitamin D" Vitamin D and osteoclastogenesis., 20 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suda,T.,et al.: "Methods in Enzymology" Role of 1α,25-dihydroxyvitamin D_3[1α,25(OH)_2D_3] in osteoclast differentiation and function., 12 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Onoe,Y.,et al.: "IL-13 and 1L-4 inhibit bone resorption by suppressing cyclooxygenase-2-dependent prostaglandin synthesis in osteoblasts." J.Immumol.156. 758-764 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jimi,E.,et al.: "Interleulin-1α activates and NF-kB like factor in osteoclast-like cells." J.Biol.Chem.271. 4605-4608 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzuki,H.,et al.: "Calcitonin-induced changes in cytoskeleton are mediated by a signal pathway associated with protein kinase A in osteoclasts." Endocrinology. 137. 4685-4690 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura,I.,et al.: "Chemical and physical properties of the extracellular matrix are required for the actin ring formation in osteoclasts." J.Bone Miner.Res.11. 1873-1879 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Chen,Q.R.,et al.: "Activation of cytosolic phospholipase A_2 by platelet-derived growth factor is essential for cyclooxygenase-2-dependnet prostaglandin E_2 synthesis in mouse osteoblasts cultured with IL-1." J.Biol.Chem.,in press. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tai,H.,et al.: "Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in interleukin-6-induced osteoclast formation." Endocrinology. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suda,T.,et al.: "Cells of bone:Osteoclast generation." Academic Press, 87-101 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suda,T.,et al.: "Vitamin D and osteoclastogenesis" Academic Press(in press), (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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