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Physiological role of prostaglandin H2 synthase-2 (COX-2) in bone metabolism

Research Project

Project/Area Number 08672119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionGraduate School, Tokyo Medical and Dental University

Principal Investigator

MORITA Ikuo  Graduate School, Tokyo Medical and Dental University, 歯学研究科, 助教授 (60100129)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsprostaglandin / PGE2 / COX / osteoclast formation / PTH / VEGF / angiogenesis / プロスタグランジン / COX-2 / 破骨細胞 / ビタミンD_3
Research Abstract

Prostaglandin E2 produced by prostaglandin H2 synthase (COX) has been to be forcused on the bone forming factor as well as bone resorbing factor. COXs have two isozymes, COX-1 and COX-2. In this study, we investigated that the physiological roles of COX-1 and COX-2 in bone metabolism. When IL-1 added to the bone marrow culture, in which stem cells can be differentiated to osteoclasts, the expression of COX-2 mRNA and protein in osteoblasts were stimulated by IL-1 and the PGE2 produced by COX-2 supported the osteoclast formation.In contrast, the osteoclast formation induced by IL-6, PTH and 1,25- (OH) 2 vitamin D3 was thought to be independent to prostaglandin synthesis, but COX inhibitor also inhibited the osteoclast formation induced by them. In this study, we also tried to be clear the mechanisms for the involvement of prostaglandins in these systems. In order to examine this, we applied the assay system for measuring COX activity in individual intact cell. The cells cultured with PTH expressed COX activity whereas the cells cultured without PTH did not express COX activity. The PG synthetic activity was observed in tartrate-resistant acid phosphatase positive mononucleated cells as well as osteoblastic cells. Moreover, the PG activity in the cells during the late phase of the culture was significantly inhibited by NS-398, a specific inhibitor of COX-2. These data indicate that the COX-2 expression in preosteoclasts is necessary for the differentiation to osteoclasts. Next, we examined the role of COX-2 in bone formation. The PGE2 produced by COX-2 stimulated VFGF production in osteoblasts, and the produced VEGF stimulated angiogenesis in the newly synthesized bone and may have the role of maintenance of bone.
In conclusion, it is clearly demonstrated in this study that COX-2 is an important enzyme for bone metabolism.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yan SP.Morita l.Murota S.: "Eicosapentaenoic acid pretreatment attenuatedthe cell proliferation response to vascular endothelial growth factor via down-regulation of KDR/Flk・1expression in bovine vascular endothelial cells." Journal of Cellular Physiology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shitashige M.Morita I.Murota S.: "Different substrate utilization beetween prostaglandin endoperoxide H synthase-1 and -2 in NIH3T3fibroblasts." Biochimica dt Biophysica Acta. 1389. 57-66 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kitamura Y.Morita I.et al.: "Effect of IL-6 on tumor cell invation of vascular endothelial monolayers." Surgery Today.27. 5334-541 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamashita H.Morita I.et al.: "Cgowth/differentiation factor-5 induces angiogenesis in vivo." Experimental Cell Research.235. 218-226 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iwamoto M.Morita I et al.: "A biotinylated perfringolysin O derivative:a new probe for detection of cell surface cholesterol." Biochimica et Biophysica Acta. 1329. 222-230 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morita I.Sato I.Ma L.Murota S: "Enhancement of membrane fluidity in cholesterol-poor endothelial cells pre-treated with simvastatin" Endothelium.5. 107-113 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gao Y,Morita I et al.: "Expression of IL-6 receptor and GP130 in mouse bone marrow cells during osteoclast differentiation" Bone. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shitashige M.Morita I.Murota S.: "Different substrate utilization between prostaglandin endoperoxide H synthase-1 and -2 in NIH3T3 fibroblasts." Biochimica et Biophysica Acta. 1389. 57-66 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamashita H.Shimizu A.Kato M.Nishitoh H.Ichijo H.Hanyu A.Morita I.Kimura M.Makishima F.Miyazono K.: "Growth/ differentiation factor-5 induces angiogenesis in vivo." Experimental Cell Research.235. 218-26 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mitsue Onodera, Ikuo Morita, Sei-itsu Murota: "Interaction between NOS and COX" Japanese Journal of Circulation Research. 20. 129-140 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Noguchi K.Morita I.et al.: "Prostaglandin production via induction of cyclooxygenase-2 by human gingival fibroblasts stimulated with lipopolysaccharides" Inflammation. 20 (5). 555-68 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato T.Morita I.et al.: "Involvement of prostaglandin endoperoxide H synthase-2 in osteoclast-like cell formation induces by interleukin-1 beta." Joutnal of Bone & Mineral Research. 11. 392-400 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Gao Y, Morita I et al.: "Expression of IL-6 receptor and GP130 in mouse bone marrow cells during osteoclast differentiation" Bone. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Shitashige M., Morita I., Murota S.: "Defferent substrate utilization between prostaglandin endoperoxide H synthase-1 and -2 in NIH3T3 fibroblasts." Biochimica et Biophysica Acta. 1389. 57-66 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamashita H., Morita I.et al.: "Growth / differentiation factor-5 induces angiogenesis in vivo." Experimental Cell Research.235. 218-226 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小野寺光江、森田育男、室田誠逸: "NOSとCOXの相互作用" 血管. 20(3). 129-140 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Noguchi K., Morita I.et al.: "Prostaglandin production via induction of cyclooxygenase-2 by human gingival fibroblasts stimulated with lipopolysaccharides." Inflammation.20. 55-68 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato T., Morita I.et al.: "Involvement of prostaglandin endoperoxide H synthase-2 in osteoclast-like cell formation induced by interleukin-1 beta." Journal of Bone & Mineral Research.11. 392-400 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Sato,I.Morita et al.: "Involvement of prostaglandin endoperoxide H synthase-2 in osteoclast-like cell formation induced by interleukin-1b" J Bone Mineral Res. 11. 392-400 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Sato,I,Morita et al.: "Prostaglandin E2 mediates parathyroid hormone induced osteoclast formation by cyclic AMP independent mechanism" Adv PG TX LT Res. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Morita,I.,et al.: "A novel method for prostaglandin endoperoxide H synthase activity in individual intact cell" Adv PG TX LT Res. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Tokushima,T.Sato,I.Morita,et al.: "Involvement of prostaglandin endoperoxide H in osteoclast formation induced by parathyroid hormone" Adv PG TX LT Res. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 平田結喜緒,森田育男: "NOSとCOX" メディカルレビュー社, 193 (1996)

    • Related Report
      1996 Annual Research Report

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

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