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骨芽細胞の分化調節機構を基盤として新しい骨再生療法を開発する

Research Project

Project/Area Number 12137208
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Medical and Dental University (2004)
Nagasaki University (2000-2003)

Principal Investigator

山口 朗  東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (00142430)

Co-Investigator(Kenkyū-buntansha) 勝部 憲一  東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (20233760)
坂本 啓  東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (00302886)
塚崎 智雄  長崎大学, 大学院・医歯薬学総合研究科, 助教授 (50315230)
柴田 恭明  長崎大学, 大学院・医歯薬学総合研究科, 助手 (80253673)
藤田 修一  長崎大学, 大学院・医歯薬学総合研究科, 助手 (00181355)
高橋 弘  長崎大学, 歯学部, 助教授 (20124597)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥53,500,000 (Direct Cost: ¥53,500,000)
Fiscal Year 2004: ¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2003: ¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2002: ¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥12,800,000 (Direct Cost: ¥12,800,000)
Keywords骨芽細胞 / 骨形成 / 骨再生 / Runx2 / 間葉系幹細胞 / BMP / 細胞移植 / GFP / 再生 / 再生療法 / 細胞分化
Research Abstract

A)間葉系幹細胞の性状の解析及び分離・移植法の確立
・ヒト過誤腫よりSV40LargeT抗原導入により単一細胞に由来し、骨芽細胞、軟骨細胞、脂肪細胞、骨格筋、平滑筋への分化能を保持する細胞株CloneKを樹立した(Cell Tissue Res 317:237-246,2004)
・ヒト軟骨肉腫から樹立した細胞株USACは軟骨細胞、骨芽細胞、脂肪細胞への分化能を保持しており、この細胞がヒト間葉系細胞の分化過程の解析に有用なことを報告した(BONE 34:648-655,2004)。
B)骨芽細胞の分化を調節する転写因子群の機能の解析
・骨芽細胞の分化過程及び骨形成過程Notchシグナルの重要性を明らかにした(J.Biol.Chem. (in press))
・骨格形成で重要な役割を担うMsx2はBMP-2の骨芽細胞の分化を促進し、脂肪細胞の分化を抑制することを明らかにした(Mol Cell Biol. 25:1971-1979,2005)。
C)解析結果を臨床応用するための基礎研究
・GFPトランスジェニックマウスから採取した細胞を野生型の骨欠損部に移植する実験系を確立し、生体内で移植細胞の運命を追跡できる実験系を確立した。また、BMP-2を過剰発現した皮膚線維芽細胞の移植が骨再生に有用なことを明らかにした(Bone 32:502-512,2003、BONE 34:993-1003,2004)。
・9.4-T magnetic resonance (MR)が骨格の解析に有用なことを示した(BONE 34:619-628,2004)。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All 2005 2004 Other

All Journal Article (6 results) Publications (24 results)

  • [Journal Article] CCAAT/enhancer binding protein β isoform, LIP, regulates ommitment of osteoblasts and adipocytes.2005

    • Author(s)
      Hata K, Yamaguchi A, et al.
    • Journal Title

      Mol Cell Biol. 25

      Pages: 1971-1979

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Critical regulation of BMP-induced osteoblastic differentiation by Delta1/Jagged 1-activated Notch 1 signaling.2005

    • Author(s)
      Nobuta M, Tsukazaki, Yamaguchi A, et al.
    • Journal Title

      J.Biol.Chem. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reciprocal roles of Msx2 in regulation of osteoblast and adipocyte differentiation2004

    • Author(s)
      Ichida F, Nishimura R, Yamaguchi A, Yoneda T., et al.
    • Journal Title

      J Biol Chem 279

      Pages: 34015-34022

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice.2004

    • Author(s)
      Kadowaki A, Yamaguchi A, et al.
    • Journal Title

      BONE 34

      Pages: 993-1003

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Establishment of a clonal human mesenchymal cell line that retains multilineage differentiation capacity from a spinal hamartoma.2004

    • Author(s)
      Doiguchi Y, Yamaguchi A, et al.
    • Journal Title

      Cell Tissue Res 317

      Pages: 237-246

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of a new member of IGFBP superfamily, IGFBP-rP10, in proliferation and differentiation of osteoblastic cells.2004

    • Author(s)
      Shibata Y, Yamaguchi A, et al.
    • Journal Title

      Biochem Biophys Res Commun 325

      Pages: 1194-1200

    • Related Report
      2004 Annual Research Report
  • [Publications] Ochi K, Chen G, Ushida T, Gojo S, Segawa K, Tai H, Ueno K, Ohkawa H, Mori T, Yamaguchi A, Toyama Y, Hats J, Umezawa A: "Use of mature osteoblasts in abundance act as desired -shaped bone regeneration in combination with a modified poly DL-Lactic-co-glycolic acid (PLGA)-collagen sponge."J Cell Physiol. 194. 45-53 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shirota T, Tashiro M, Ohno K, Yamaguchi A: "Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats."J Oral Maxillofac Surg. 61. 471-480 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirata K, Tsukazaki T, Kadowaki A, Furukawa K, Shibata Y, Moriishi T, Okubo Y, Bessho K, Komori T, Mizuno A, Yamaguchi A: "Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2."BONE. 32. 502-512 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iioka T, Furukawa K, Yamaguchi A, Shindo H, Yamashirta S, Tsukazaki T: "p300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the con served lysine residue adjacent to the homeodomain."J.Bone Miner.Res.. 18. 1419-1429 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shindo K, Kawashima N, Sakamoto K, Yamaguchi A, Umezawa A, Takagi M, Katsube K, Suda H.: "Osteogenic differentiation, of the mesenchymal progenitor cells, Kusa is suppressed by Notch signaling."Exp Cell Res. 290. 370-380 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] A.Kadowaki, T.Tsukazaki, K.Hirata, Y.Shihata, Y.Okubo, K.Bessho, T.Komori, N.Yoshida, A.Yamaguchi: "Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice"BONE. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirata K, Tsukazaki T, Yamaguchi A, et al.: "Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2"BONE. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ochi K, Chen G, Yamaguchi A, Umezawa A, et al.: "Use of mature osteoblasts in abundance act as desired -shaped bone regeneration in combination with a modified poly DL-Lactic-co-glycolic acid (PLGA)-collagen sponge"J.Cell.Physiol.. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuasa T, Kataoka H, Kinto N, Shibata Y, Yamaguchi A, et al.: "Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP-2"J.Cell.Physiol.. 193. 225-232 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furukawa K, Yamaguchi A, Tsukazaki T, et al.: "Functional domains of paired-like homeoprotein Cart1 and the relationship between dimerization and transcription activity"Genes Cells. 11. 1135-1147 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shibata Y, Yamaguchi A, Koji T, et al.: "Inhibition apoptosis and possible involvement of Fas/Fas ligand to avoid apoptosis of minor salivary gland in Sjogren's syndrome"Hum.Cell. 15. 52-60 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Merida LM, Yamaguchi A, Kawai S, et al.: "Effects of vitamin D analog, 22-oxa-1,25 dihydroxyvitamin D3, on bone reconstruction by vascularized bone allograft"BONE. 30. 422-427 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kusafuka K, et al.: "Cartilage-specific matrix protein chondromodulin-I is associated with chondroid formation in salivary pleomorphic adenomas : immunohistochemical analysis"Am. J. Pathol.. 158. 1465-1472 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kusafuka K, et al.: "Ossification of tracheal cartilage in aged humans : a histological and immuno-histochemical analyssis"J. Bone Miner. Metab.. 19. 168-174 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamura T, et al.: "The effects of transplantation of osteoblastic cells with BMP/carrier complex on bone repair"BONE. 29. 169-175 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Liu W, et al.: "Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures"J. Cell Biol.. 155. 157-166 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Merida LM, et al.: "Effects of vitamin D analog, 22-oxa-1,25 dihydroxyvitamin D3, on bone reconstruction by vascularized bone allograft"BONE. 30. 422-427 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shibata S,Fujita S,Takahashi H,Yamaguchi A,Koji T: "Assessment of decalcifying protocols for detection of specific RNA by nonradioactive in situ hybridization in calcified tissues."Histochem.Cell Biol.. 113. 153-159 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi H,Gao Y-H,Ueta C,Yamaguchi A,Komori T: "Multilineage differentiation of Cbfa1-deficient calvarial cells in vitro."Biochem.Biophys.Res.Commun.. 273. 630-636 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto-Iwamoto M,Nakamura T,Aikawa T,Higuchi Y,Yuasa T,Yamaguchi A,Nohno T,Noji S,Matsuya T,Kurisu K,Koyama E,Pacifici M,Iwamoto M: "Hedgehog proteins induce chondrogenic cell differentiation and cartilage formation."J.Bone Miner.Res.. 15. 1659-1668 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kataoka H,Ochi M,Enomoto K,Yamaguchi A: "Cloning and embryonic expression patterns of the zebrafish Runt domain genes, runxa and runxb."Mech Dev. 98. 139-143 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamaguchi A,Komori T,Suda T: "Regulation of Osteoblast Differentiation Mediated by BMPs, Hedgenhogs and Cbfa1."Endocrine Reviews. 21. 393-411 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山口朗(分担執筆): "骨形成と骨再生・先端医療シリーズ・歯科医学2:「歯周病-新しい治療を求めて」"岡田宏,石川烈,村山洋二監修. 1-7 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamaguchi A(分担執筆): "Regulatory mechanism of osteoblast differentiation. In : Tissue Engineering for Therapeutic Use 4"Y.Ikada and Y.Shimizu (eds). 75-81 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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