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Effect of VEGF's on osteockast formation and activation

Research Project

Project/Area Number 13671950
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YAMADA Shoji  Showa Univ., Dept., of Pharma, Professor, 歯学部, 教授 (00111617)

Co-Investigator(Kenkyū-buntansha) SAKAI Nobuhiro  Showa Univ., Dept., of Pharma, assistant, 歯学部, 助手 (90286849)
SUZUKI Keiko  Showa Univ., Dept., of Pharma, assistant Prof., 歯学部, 講師 (50119187)
AMANO Hitoshi  Showa Univ., Dept., of Pharma, assistant Prof., 歯学部, 講師 (90212571)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsVEGF / Flt-1 / CSF-1 / osteoclast / resorption / culture / Flk-1 / TRAP / CSF-1^<op / op>マウス / VEGF受容体1型 / op / opマウス / 偽足 / 細胞伸展 / 可溶型受容体
Research Abstract

Vascular endothelial growth factor (VEGF) is a key mediator of physiological angiogenesis. This cytokine binds to two cell surface receptors which are encoded by flt-1 or flk-1/KDR that also belong to the tyrosine kinase receptor family. Only the Flt-1 is expressed on macrophage monocyte lineage. In the present study, we investigated that whether the effect of VEGF treatment on the osteoclast differentiation in vitro. Bone marrow cells and spleen cells were obtained from 5-to 8-week-old male ddy miceor op/op mice. Non adherent G10-passed cells were cultured in & alpha-MEM with 15% FBS, 100 ng/ml RANKL, 20 ng/ml GSF-1 or 100 ng/ml VEGF. After culture for 7 days, smaller size of TRAP positive multinucleated cells were observed in the presence of RANKL and VEGF from bone marrow cells and spleen cells(Wt & op), as well as resorption pits were found than that of in the presence of RANKL and CSF-1. Treatment with Flt-1/Fc chimera, and anti VEGF antibody inhibit the RANKL and VEGF-induced osteoclast differentiation but neutralizing anti-CSF-1 Receptor antibody did not. In addition, Flt-1 was detected by immunocytochemical study with anti-Flt-1 antibody but not Flk-1 on osteoclast and its precursors. These results suggest that VEGF has important role in osteoclast differentiation and bone resorption system as well as CSF-1.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Zhu B, Suzuki K, Goldberg HA, Rittling SR, Denhardt DT, McCulloch CA, Sodek J: "Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors : evidence of a role for an intracellular form of osteopontin."J Cell Physiol.. 198・1. 155-167 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 天野均, 高橋勝彦: "骨とp57^<Kip2>遺伝子"日骨形態計測. 14・1. 9-13 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori H, Sakai H, Morihata H, Kawawaki J, Amano H, Yamano T, Kuno: "Regulatory mechanisms and physiological relevance of a voltage-gated H+ channel in murine osteoclasts : phorbol myristate acetate induces cell acidosis and the channel activation."J Bone Miner Res.. 18・11. 2069-2076 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirama Y, Morohashi T, Sano T, Maki K, Ohta A, Sakai N, Yamada S, Sasa R.: "Fructooligosaccharides prevent disorders of the femoral neck following gastrectomy in growing rats."J Bone Miner Metab.. 21・5. 294-298 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujita D, Yamashita N, Iita S, Amano H, Yamada S, Sakamoto K: "Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells."Prostaglandins Leukot Essent Fatty Acids.. 68・5. 351-358 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hosoi T, Yoda T, Yamaguchi M, Amano H, Orimo H: "Elderly women with oral exostoses had higher bone mineral density."J Bone Miner Metab.. 21・2. 120-122 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi H., Amano H., Yamada S.: "Putative role of basement membrane for dentinogenesis in the mesenchyme of murine dental papillae in vitro."Cell Tissue Res.. vol.303. 93-107 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hisamitsu T., Ohata H., Kawanishi T., Iwamoto T., Shigekawa M., Amano H., Yamada S., Momose K.: "A mechanism of Ca^<2+> release from Ga2+ stores coupling to the Na^+/Ga^<2+> exchanger in cultured smooth muscle cells."Life Science. Vol.69. 2775-2787 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K, Zhu B, Rittling SR, Denhardt DT, Goldberg HA, McGulloch CA, Sodek J.: "Golocalization of intracellular osteopontin with CD44 is associated with migration, cell fusion, and resorption in osteoclasts."J Bone Miner Res.. vol.17. 1486-1497 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K, Yamada S.: "Ascites Sarcoma 180 secretes a soluble factor(s) which inhibits mineralized formation in vitro."vol.20. 186-195 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano H: "The specifity of bone resorption process in the maxilla and the mandibule."CLINICAL CALSIUM. vol.12. 93-97 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morohashi T, Hirama Y, Takahara S, Sano T, Saitoh S, 0hta A, Sasa R, Yarnada S.: "Defects in mandibular bone area, enamel iron content and dentine formation following gastrectomy in rats."Arch Oral Biol.. vol.47. 499-504 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hosoi T, Yoda T, Yamaguchi M, Amano H, Orimo H.: "Elderly women with oral exostoses had higher bone mineral density."J Bone Miner Metab.. Vol.21. 120-122 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujita D, Yamashita N, Iita S, Amano H, Yamada S, Sakamoto K.: "Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells. Prostaglandins"Leukot Essent Fatty Acids.. Vol.68. 351-358 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori H, Sakai H, Monihata H, Kawawaki J, Amano H, Yamano T, Kuno: "Regulatory mechanisms and physiological relevance of a voltage-gated H^+ channel in murine osteoclasts: phorbol myristate acetate induces cell acidosis and the channel activation."J.Bone Miner Res.. vol.18. 2069-2076 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhu B, Suzuki K, Goldberg HA, Rittling SR, Denhardt DT, McCulloch GA, Sodek J.: "Osteopontin modulates GD44-dependent chemotaxis of penitoneal macrophages through G-protein-coupled receptors: evidence of a role for an intracellular form of osteopontin."J Cell Physiol.. Vol.198. 155-167 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhu B, Suzuki K, Goldberg HA, Rittling SR, Denhardt DT, McCulloch CA, Sodek J.: "Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through G-protein-coupled receptors : evidence of a role for an intracellular form of osteopontin."J Cell Physiol.. 198・1. 155-167 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 天野均, 高橋勝彦: "骨とp57Kip2遺伝子"日骨形態計測. 14・1. 9-13 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mori H, Sasaki H, Morihata H, Kawawaki J, Amano H, Yamano T, Kuno: "Regulatory mechanisms and physiological relevance of a voltage-gated H+ channel in murine osteoclasts : phorbol myristate acetate induces cell acidosis and the channel activation"J Bone Miner Res.. 18・11. 2069-2076 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirama Y, Morohashi T, Sano T, Maki K, Ohta A, Sakai N, Yamada S, Sasa R.: "Fructooligosaccharides prevent disorders of the femoral neck following gastrectomy in glowing rats."J Bone Miner Metab.. 21・5. 294-298 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujita D, Yamashita N, Iita S, Amano H, Yamada S, Sakamoto K.: "Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells."Prostaglandins Leukot Essent Fatty Acids. 68・5. 351-358 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hosoi T, Yoda T, Yamaguchi M, Amano H, Orimo H.: "Elderly women with oral exostoses had higher bone mineral density."J Bone Miner Metab.. 21・2. 120-122 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 信川真智子, 山田庄司, 天野均: "破骨細胞形成に及ぼすジクロフェナックナトリウムの影響"歯科薬物療法. 20・3(印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki K, Yamada S.: "Ascites Sarcoma 180 secretes a soluble factor(s) which inhibits mineralized formation in vitro"歯科薬物療法. 20・3(印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki S., Zhu B., Sodeck J., et al.: "Migration and resorptive activity is impaired in osteoclasts derived from OPN-/-and CD44-/-mice"J.Bone Miner.Res.. 17(印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] Hisamitsu T, Amano H, Yamada S, Momose K, et al.: "A mechanism of Ca^<2+> release from Ca^<2+> stores coupling to the Na^+/Ca^<2+> exchanger in cultured smooth muscle cells"Life Science. 69・23. 2775-2787 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 天野均, 鈴木恵子, 山田庄司: "破骨細胞におけるNa^+/Ca^<2+>交換体(NCX)の役割に関する研究"昭歯誌. 21・1. 82-85 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kikuchi H., Amano H., Yamada S.: "Putative role of basement membrane for dentinogenesis in the mesenchyme of murine dental papillae in vitro"Cell Tissue Res.. 303・1. 93-107 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 信川真智子, 山田庄司, 天野均: "破骨細胞形成に及ぼすジクロフェナックナトリウムの影響"歯科薬物療法. 20・3(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki K, Yamada S.: "Ascites Sarcoma 180 secretes a soluble factor(s) which inhibits mineralized formation in vitro"歯科薬物療法. 20・3(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki S., Zhu B., Sodeck J., et al.: "Migration and resorptive activity is impaired in osteoclasts derived from OPN-/- and CD44-/- mice"J.Bone Miner.Res.. 17(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hisamitsu T, Amano H, Yamada S, Momose K., et al.: "A mechanism of Ca^<2+> release from Ca^<2+> stores coupling to the Na^+/Ca^<2+> exchanger in cultured smooth muscle cells"Life Science. 69・23. 2775-2787 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 天野均, 鈴木恵子, 山田庄司: "破骨細胞におけるNa^+/Ca^<2+>交換体(NCX)の役割に関する研究"昭歯誌. 21・1. 82-85 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kikuchi H., Amano H., Yamada S.: "Putative role of basement membrane for dentinogenesis in the mesenchyme of murine dental papillae in vitro"Cell Tissue Res.. 303・1. 93-107 (2001)

    • Related Report
      2001 Annual Research Report

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

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