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Functional analysis of transcriptional regulator induced by ODF in the signal transduction of formation and activation of osteoclasts

Research Project

Project/Area Number 13671942
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionSaga Medical School

Principal Investigator

KUKITA Akiko  Saga Medical School, Medicine, Associate Professor, 医学部, 助教授 (30153266)

Co-Investigator(Kenkyū-buntansha) KUKITA Toshio  Saga Medical School, Dentistry, Associate Professor, 大学院・歯学研究院, 助教授 (70150464)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsosteoclast / differentiation / macrophage / histone deacetylate inhibitor / 転写因子
Research Abstract

(1) Analysis of role of OCZF in the signal transduction of osteoclastogenesis
OCZF inhibit transcriptional activity of macrophage transcriptional factor, egr-1. Histone deacetylase inhibitor, trichostatin A (TSA) inhibits transcriptional repressive activity of OCZF. TSA and a another histone deacerylase inhibitor, sodium butyrate, NaB inhibited osteoclast differentiation. On the other hand, TSA and NaB did not have the effect on the differentiation into macrophages. In a macrophage cell line, RAW 264 which is able to differentiate into osteoclasts by the addition of RANKL, TSA and NaB inhibited the translocation of NFkappaB into nucleus and phospholylation of MAPK, whose are regulators of osteoclastogenesis. Data suggest the target genes of T5A and NaB may be regulated by OCZF and involved in the signal transduction of osteoclastogenesis.
Stimulative activity of NFkB of OCZF was analyzed. OCZF did not affect the binding activity to this consensus sequence. On the other hand, we found OCZ … More F stimulated the transcription from the reporter plasmids which have promoter region of p21 and p27, cyclin-dependent kinase (CDK) inhibitors whose expression is stimulated by ODF in osteoclastogenesis. Difference of the expression of protein and mRNA between macrophage cell, RAW264 expressing OCZF and control was compared by western analysis and DNA microarray.
(2) Analysis of OCZF expression by in situ hybridization of rat adjuvant arthritis.
In situ hybridization analysis revealed that OCZF is strongly expressed in osteoclasts and some cells in germinal center.
(3) Analysis of signaling molecules interacting with OCZF
We isolated RNA and prepared cDNA expressed in RAW 264 cells and are analyzing some genes which are possibly interacting with OCZF with yeast two-hybrid system. At same time we establish the cell line in which the expression of OCZF is regulated by tetracycline. Using the cell lines, we are going to find out the molecules which interact with OCZF by immunoprecipitation methods. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] M.Komine: "Tumor necrosis factor-alpha cooperates with receptor activator of nuclear factor KappaB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture"Bone. 28. 474-483 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Kukita: "Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions"Journal of Endocrinology. 170. 175-183 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Hossain: "Balance of Th1/Th2 cytokines associated with the preventive effect of incomplete Freund's adjuvant on the development of adjuvant arthritis in LEW rats"J Autoimmun.. 17. 289-295 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Sakai: "Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplasty induce osteoclast differentiation, as do stromal cells"Ann Rheum Dis.. 61. 103-109 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] CL.Zheng: "Complete Freund's adjuvant suppresses the development and progression of pristane-induced arthritis in rats"Clin Immunol.. 103. 204-209 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Kukita: "The new aspect of calcitonin escape phenomenon : a possible involvement of osteoclast differentiation antigen in the regulation of osteoclastogenesis and function of calcitonin receptor. (review article)"Recent Research Developments in Endocrinology/Transworld Research Network. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Rahman: "Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages"Blood. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Komine, A. Kukita, T. Kukita, Y. Ogata, T.Hotokebuti, O. Kohashi: "Tumor necrosis factor alpha cooperates with receptor activator of nuclear factor kappaB ligand in generation of osteoclasts in stromal cell depleted rat bone marrow cell culture"Bone. 28. 474-483 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Kukita, A. Kukita, T. Watanabe and T. Iijima: "Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin- regulated conditions"Journal of Endocrinology. 170. 175-183 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A. Hossain, CL. Zheng, A. Kukita, and O. Kohashi: "Balance of Th1/Th2 cytokines associated with the preventive effect of incomplete Freund's adjuvant on the development of adjuvant arthritis in LEW rats."J Autoimmun.. 17(4). 289-295 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Sakai, S. Jingushi, T. Shuto, K. Urabe, T. Ikenoue, K. Okazaki, T. Kukita, A. Kukita, and Y. Iwamoto: "Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplasty induce osteoclast differentiation, as do stromal cells"Ann Rheum Dis... 61(2). 103-109 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] CL. Zheng, MA. Hossain. A. Kukita. K. Ohki K, T. Satoh, and O. Kohashi: "Complete Freund's adjuvant suppresses the development and progression of pristane-induced arthritis in rats."Clin Immunol.. 103(2). 204-209 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Kukita and A. Kukita: "The new aspect of calcitonin escape phenomenon-a possible involvement of osteoclast differentiation antigen in the regulation of osteoclastogenesis and function of calcitonin receptor. (review article) Recent Research Developments in Endocrinology/ Transworld Research Network"Recent Research Developments in Endocrinology/ Transworld Research Network. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Rahman, A. Kukita, T. Kukita, T. \shobuike, T. Nakamura and O. Kohashi: "Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages."Blood. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Hossain: "Balance of Th1/Th2 ajtokines associated with the preventive effect of incomplete Freund's adjuvant on the development of adjuvant arthritis in LEW rats"J. Autoimmum. 17・4. 289-295 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Sakai: "Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplastry induce osteoclast differentiation, as do stromal cells"Ann Rheum Dis.. 61・2. 103-109 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Cl.Zheng: "Complete Freund's adjuvant suppresses the development and progression of pristane-induced arthritis in rats"Clin. Immunol.. 103・2. 204-209 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Kukita: "Function of transaiptional regulaters OCZF expressed in osteoclasts"J. Bone Min. Res.. 17(s.1). 347 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Kukita: "Modulation of osteoclastogenesis through functional adrenomeduitin receptors expressed on osteoclast precursors, that is partly related to osteoclast differentiation artigen"J. Bone. Min Res.. 17(s.1). 347 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Rahman: "Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophage"Blood. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Komine: "Tumor necrosis factor-α cooperates with receptor activator of nuclear factor KB ligand in generation of asteoclasts in stromae coll-depleted rat bone marrow coll culture"Bone. 28・5. 474-483 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kukita: "Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, isinvolvod in osteoclastogenesis under calcitonin-regulated conditions"Journal of Endocrinology. 170. 175-183 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kukita: "Katl-antigen areliable immunological marker for identifying osteodast precursors of rats : detection of subpopulations a mong precursors and initiation of osteoclastogeresis"Histochem Cell Biol. 115. 215-222 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kukita: "The new aspect of calcitonin escape the nomenorv : apcssikle inuuivement of asteoclast differentiation antigen in the regulation of osteoclastogenesis and function of caluitonein receptor"Recent Resecnch Developments in Endocrinology/Transworld Research Network. (in press). (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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