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The Role of Cytokines in Bone Resorption and Bone Formation

Research Project

Project/Area Number 01480436
Research Category

Grant-in-Aid for General Scientific Research (B)

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

Principal Investigator

ABE Etsuko  Showa Univ., School of Dentistry Associate Professor, 歯学部, 助教授 (70119147)

Co-Investigator(Kenkyū-buntansha) HE Jin Cheng  Showa Univ., School of Dentistry Assistant, 歯学部, 助手 (10205049)
TAKAHASHI Naoyuki  Showa Univ., School of Dentistry Lecturer, 歯学部, 講師 (90119222)
SUDA Tatsuo  Showa Univ., School of Dentistry Professor, 歯学部, 教授 (90014034)
TANAKA Hirofumi  Showa Univ., School of Dentistry Assistant (30146899)
宮浦 千里  昭和大学, 歯学部・生化学教室, 助手 (20138382)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1990: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥4,500,000 (Direct Cost: ¥4,500,000)
KeywordsOsteoblast / Osteopontin / Interleukin 1 / Bone resorption / LIF / Macrophage fusion / Lalpha, 25 (OH) _2D_3 / GM-CSF / 細胞融合 / 活性型ビタミンD / GMーCSF / Iγ-4 / Iγ-6
Research Abstract

Experiment 1 : It is known that most bone-resorbing agents including 1alpha, 25 (OH) _2D_3, interleukin 1 (IL-1) and tumor necrosis factor (TNF) first act on osteoblasts to induce osteoclastic bone resorption. We there for examined novel proteins produced by osteoblasts in response to those bone resorbing agents. We also examined the mechanism of regulation of trascription and translation of inter-leukin 6 (IL-6) and leukemia inhibitory factor (LIF) in osteoblasts in response to bone-absorphon agents.
[Methods] A mouse osteoblastic cell line (E1) and mouse primary osteoblasts were cultured for 3 days with various bone-resorbing agents. After incubation, conditioned media and cells were collected for determining protein contents and mRNA levels of IL-6 and LIF. To explore novel proteins produced by osteoblasts in response to bone-resorbing agents, E1 cells were cultured for 3 days with [^<35>S] -methio- nine in the presence of 1alpha, 25 (OH) _2D_3 and conditioned media were analyzed by … More SDS-PAGE.
[Results] IL-1, TNF and lypopolysaccharides (LPS) greatly increased mRNA levels of IL-6 and LIF both in E1 cells and primary osteoblasts and increased production of IL-6 by E1 cells. Both recombinant IL-6 and LIF stimulated bone-resorbing activity at higher doses. Simultaneous addition of the two cytokines showed similar bone-resorbing activity at much lower doses. 1alpha, 25 (OH) _2D_3 induced 68 kDa and 116 kDa proteins under a reducing condition in E1 cells. The 68 kDa protein appeared to be identical with osteopontin, since the molecular weight and the regulation pattern by 1alpha, 25 (OH) _2D_3 were similar. Purification of the 116 kDa protein and analysis of the N-terminal amino acid sequence are in progress.
Experiment 2 : We have reported that 1alpha, 25 (OH) _2D_3, interleukin 4 (IL-4) and a macrophage fusion factor (MFF) present in conditioned medium of mouse spleen cells treated with concanavalin A similarly induce fusion of mouse alveolar macrophages. In this experiment, we examined the mechanism of fusion induced by 1alhpa, 25 (OH) _2D_3 and identified MFF.
[Methods] Mouse alveolar macrophages were treated with 1alpha, 25 (OH) _2D_3 for appropriate times in various concentrations of medium calcium to determine the condition for inducing macrophage fusion. After incubation with 1alpha, 25 (OH) _2D_3, a calcium-dependent protein, transglutaminase, was detected by western blot analysis. To determine the nature of MFF, the medium content of various cytokines was measured and neutralized by adding various antibodies.
[Results] 1alpha, 25 (OH) _2D_3 induced macrophage fusion at medium calcium concentration higher than 2 mM. The vitamin also induced transglutaminase time-dependently. It was concluded by the neutralization experiments with the antibodies that MFFs in the conditioned emdium of spleen cells were IL-4 and GM-CSF. Less

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Jin,C.H.: "Fusion of mouse alveolar macrophages induced by 1α,25ーdihydroxyvitamin D_3 involves extracellular, but not intracellular calcuium." J.Cell.Physiol.142. 434-439 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Jin.C.H.: "Interleukin 1 regulates the expression of osteopontin mRNA by osteoblasts." Mol.Cell.Endocrinol.74. 221-228 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ishimi,Y.: "ILー6 is produced by osteoblasts and induces bone resorption." J.Immunol.145. 3297-3303 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Tanaka,H.: "Transglutaminase is involved in the fusion of mouse alveolar macrophages induced by 1α,25ーdihydroxyvitamin D_3." Exp.Cell Res.192. 165-172 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Cheng He Jin, et al.: "Fusion of mouse alveolar macrophages induced by 1apha, 25-dihydroxy- vitamin D_3 involves extracellular, but not intracellular calcium." J. Cell. Physiol.142. 434-439 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Cheng He Jin, et al.: "Interleukin 1 regulates the expression of soteopontin mRNA by osteoblasts." Mol. Cell. Endocrinol.74. 221-228 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yoshiko Ishimi, et al.: "IL-6 is produced by osteoblasts and induces bone resorption." J. Immunol.145. 3297-3303 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hirofumi Tanaka, et al(.: "Transglutaminase is involved in the fusion of mouse alveolar macrophages induced by 1alpha, 25-dihydroxyvitamin D_3." Exp. Cell Res.192. 165-172 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Jin,C.H.: "Fusion of mouse alveolar macrophages induced by 1α,25ーdihydroxyvitamin D_3 involves extracellular,but not intracellular calcium." J.Cell.Physiol.142. 434-439 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Jim,C.H.: "Interleukin 1 regulates the expression of osteopontin mRNA by osteoblasts." Mol.Cell.Endocrinol.74. 221-228 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ishimi,Y.: "ILー6 is produced by osteoblasts and induces bone resorption." J.Immunol.145. 3297-3303 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tanaka,H.: "Transglutaminase is involved in the fusion of mouse alveolar macrophages induced by 1α,25ーdihydroxyvitamin D_3" Exp.Cell Res.192. 165-172 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Jin,C.H.: "The fusion of mouse alveolar macrophages induced by 1α,25ーdihydroxyvitamin D_3 involves extracellular,but not intracellular,calcium." Journal of Cellular Physiology. in press. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suda,T.: "The role of vitamin D in bone and intestinal cell differentiation." Annual Review Nutrition.10. 195-211 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Suda,T.: "Role of veitamin D in osteoclast fromation." Advances in Endocrinology. 6. 25-35 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Tanaka,H.: "Spermidineーdependent proteins are involved in the fusion of mouse alveolar macrophages induced bt 1α,25ーdihydroxyーvitamin D_3 and interleukin 4." Experimental Cell Research. 180. 72-83 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Miyaura,C.: "Production of interleukin 6 and its relation to the macrophage differentiation of mouse myeloid leukemia cells(Ml)treated with differentiationーinducing factor and 1α,25ーdihydroxyvitamain D_3" Biochemical and Biophysical Research Communications. 158. 660-666 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Jin,C.H.: "Calcium is essential in the fusion of mouse alveolar macrophages induced by 1α,25ーdihydroxyvitamin D_3." Journal of Cellular Physiology. 137. 110-116 (1988)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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