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1997 Fiscal Year Final Research Report Summary

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
Keywordsprostaglandin / PGE2 / COX / osteoclast formation / PTH / VEGF / angiogenesis
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-16  

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