軟骨内骨化を統合的に制御する分子ネットワークの解明

2009 年度 研究成果報告書

• 研究課題/領域番号: 18209047
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 整形外科学
• 研究機関: 東京大学
• 研究代表者: 川口 浩 東京大学, 医学部附属病院, 准教授 (40282660)
• 研究分担者: 鄭 雄一 東京大学, 大学院・工学系研究科, 教授 (30345053) ; 中村 耕三 東京大学, 医学部附属病院, 教授 (60126133) ; 池田 敏之 東京大学, 医学部附属病院, 特任助教 (80322759) ; 齋藤 琢 東京大学, 医学部附属病院, 特任助教 (30456107)
• 研究期間 (年度): 2006 – 2009
• キーワード: 骨 / 軟骨代謝学

研究概要

軟骨細胞の発生分化に必須である転写因子SOXファミリーのうち、SOX6を強力に誘導する分子として転写因子p63を同定した。本研究ではp63があらゆる分化段階の軟骨細胞に発現し、p63をノックアウトすると四肢の軟骨細胞の発生分化が著しく抑制されること、軟骨の初期分化や軟骨基質産生、増殖、骨組織への置換などあらゆるステップに重要であることなどを、マウスや培養細胞を用いた解析によって明らかにした。

研究成果

• [雑誌論文] Aktl in murine chondrocytes controls cartilage calcification during endochondral ossification under physiologic and pathologic conditions (2010)
  • 著者名/発表者名: Fukai A, Kawamura N, Saito T, Oshima Y, Ikeda T, Kugimiya F, Higashikawa A, Yano F, Ogata N, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: Arthritis Rheum 62(3) ページ: 826-36
• [雑誌論文] Mechanisms underlying catabolic and anabolic functions of parathyroid hormone on bone by combination of culture systems of mouse cells (2010)
  • 著者名/発表者名: Shinoda Y, Kawaguchi H, Higashikawa A, Hirata M, Miura T, Saito T, Nakamura K, Chung UI, Ogata N.
  • 雑誌名: J Cell Biochem. 109(4) ページ: 755-63
• [雑誌論文] Screening of chondrogenic factors with a real-time fluorescence-monitoring cell line ATDC5-C2ER : identification of sorting nexin 19 as a novel factor (2009)
  • 著者名/発表者名: Kan A, Ikeda T, Saito T, Yano F, Fukai A, Hojo H, Ogasawara T, Ogata N, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: Arthritis Rheum. 60(11) ページ: 3314-23
• [雑誌論文] Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice (2009)
  • 著者名/発表者名: Ota N, Takaishi H, Kosaki N, Takito J, Yoda M, Tohmonda T, Kimura T, Okada Y, Yasuda H, Kawaguchi H, Matsumoto M, Chiba K, Ikegami H, Toyama Y.
  • 雑誌名: Endocrinology 150(11) ページ: 4823-34
• [雑誌論文] C/EBPbeta Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57 (2009)
  • 著者名/発表者名: Hirata M, Kugimiya F, Fukai A, Ohba S, Kawamura N, Ogasawara T, Kawasaki Y, Saito T, Yano F, Ikeda T, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: PLoS One. 4(2) ページ: e4543
• [雑誌論文] Identification of the core element responsive to runt-related transcription factor 2 in the promoter of human type X collagen gene (2009)
  • 著者名/発表者名: Higashikawa A, Saito T, Ikeda T, Kamekura S, Kawamura N, Kan A, Oshima Y, Ohba S, Ogata N, Takeshita K, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: Arthritis Rheum 60(1) ページ: 166-78
• [雑誌論文] Association of occupational activity with radiographic knee osteoarthritis and lumbar spondylosis in elderly patients of population-based cohorts : a large-scale population-based study (2009)
  • 著者名/発表者名: Muraki S, Akune T, Oka H, Mabuchi A, En-Yo Y, Yoshida M, Saika A, Nakamura K, Kawaguchi H, Yoshimura N.
  • 雑誌名: Arthritis Rheum 61(6) ページ: 779-86
• [雑誌論文] The distinct role of the Runx proteins in chondrocyte differentiation and intervertebral disc degeneration : findings in murine models and in human disease (2008)
  • 著者名/発表者名: Sato S, Kimura A, Ozdemir J, Asou Y, Miyazaki M, Jinno T, Ae K, Liu X, Osaki M, Takeuchi Y, Fukumoto S, Kawaguchi H, Haro H, Shinomiya K, Karsenty G, Takeda S.
  • 雑誌名: Arthritis Rheum. 58(9) ページ: 2764-75
• [雑誌論文] Kruppel-like factor 5 causes cartilage degradation through transactivation of matrix metalloproteinase 9 (2008)
  • 著者名/発表者名: Shinoda Y, Ogata N, Higashikawa A, Manabe I, Shindo T, Yamada T, Kugimiya F, Ikeda T, Kawamura N, Kawasaki Y, Tsushima K, Takeda N, Nagai R, Hoshi K, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: J Biol Chem. 283(36) ページ: 24682-9
• [雑誌論文] Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes (2008)
  • 著者名/発表者名: Kawasaki Y, Kugimiya F, Chikuda H, Kamekura S, Ikeda T, Kawamura N, Saito T, Shinoda Y, Higashikawa A, Yano F, Ogasawara T, Ogata N, Hoshi K, Hofmann F, Woodgett JR, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: J Clin Invest. 118(7) ページ: 2506-15
• [雑誌論文] Patchedl haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity (2008)
  • 著者名/発表者名: Ohba S, Kawaguchi H, Kugimiya F, Ogasawara T, Kawamura N, Saito T, Ikeda T, Fujii K, Miyajima T, Kuramochi A, Miyashita T, Oda H, Nakamura K, Takato T, Chung UI.
  • 雑誌名: Dev Cell. 14(5) ページ: 689-99
• [雑誌論文] Association of microsomal prostaglandin E synthase 1 deficiency with impaired fracture healing, but not with bone loss or osteoarthritis, in mouse models of skeletal disorders (2008)
  • 著者名/発表者名: Yamakawa K, Kamekura S, Kawamura N, Saegusa M, Kamei D, Murakami M, Kudo I, Uematsu S, Akira S, Chung UI, Nakamura K, Kawaguchi H.
  • 雑誌名: Arthritis Rheum. 58(1) ページ: 172-83
• [雑誌論文] Aktl in osteoblasts and osteoclasts controls bone remodeling (2007)
  • 著者名/発表者名: Kawamura N, Kugimiya F, Oshima Y, Ohba S, Ikeda T, Saito T, Shinoda Y, Kawasaki Y, Ogata N, Hoshi K, Akiyama T, Chen WS, Hay N, Tobe K, Kadowaki T, Azuma Y, Tanaka S, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: PLoS One. 2(10) ページ: e1058
• [雑誌論文] Continuous activation of G alpha q in osteoblasts results in osteopenia through impaired osteoblast differentiation (2007)
  • 著者名/発表者名: Ogata N, Kawaguchi H, Chung UI, Roth SI, Segre GV.
  • 雑誌名: J Biol Chem. 282(49) ページ: 35757-64
• [雑誌論文] S100A1 and S100B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes (2007)
  • 著者名/発表者名: Saito T, Ikeda T, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: EMBO Rep. 8(5) ページ: 504-9
• [雑誌論文] Identification of a potent combination of osteogenic genes for bone regeneration using embryonic stem (ES) cell-based sensor (2007)
  • 著者名/発表者名: Ohba S, Ikeda T, Kugimiya F, Yano F, Lichtler AC, Nakamura K, Takato T, Kawaguchi H, Chung UI.
  • 雑誌名: FASEB J. 21(8) ページ: 1777-87
• [雑誌論文] Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability (2006)
  • 著者名/発表者名: Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T, Chikuda H, Maruyama Z, Komori T, Sato S, Takeda S, Karsenty G, Nakamura K, Chung UI, Kawaguchi H.
  • 雑誌名: Arthritis Rheum. 54(8) ページ: 2462-70
• [雑誌論文] Carminerin contributes to chondrocyte calcification during endochondral ossification (2006)
  • 著者名/発表者名: Yamada T, Kawano H, Koshizuka Y, Fukuda T, Yoshimura K, Kamekura S, Saito T, Ikeda T, Kawasaki Y, Azuma Y, Ikegawa S, Hoshi K, Chung UI, Nakamura K, Kato S, Kawaguchi H.
  • 雑誌名: Nat Med. 12(6) ページ: 665-70
• [雑誌論文] Transcriptional regulation of endochondral ossification by HIF-2α during skeletal growth and osteoarthritis development
  • 著者名/発表者名: Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H.
  • 雑誌名: Nat Med (in press)
• [雑誌論文] GSK-3beta controls osteogenesis through regulating Runx2 activity
  • 著者名/発表者名: Kugimiya F, Kawaguchi H, Ohba S, Kawamura N, Hirata M, Chikuda H, Azuma Y, Woodgett JR, Nakamura K, Chung UI.
• [学会発表] Molecular backgrounds of cartilage degeneration during os teoarthritis progression (Special Lecture : OARSI-KORS Cosponsored Symposium) (2009)
  • 著者名/発表者名: Kawaguchi H
  • 学会等名: The 35^<th> Annual Meeting of the Korean Orthopaedic Research Society
  • 発表場所: Seoul, Korea
  • 年月日: 2009-10-14
• [学会発表] Transcriptional regul ation of osteoarthritis progression (2008)
  • 著者名/発表者名: Kawaguchi H
  • 学会等名: The 13th Congress of the Asia Pacif is League of Associations for Rheuma tology (APLAR 2008)
  • 発表場所: Yokohama
  • 年月日: 20080923-20080927
• [学会発表] p63 Plays a Centr al Role in Cartilage Development by Directly Regulating Key Genes for Ch ondrogenesis (2007)
  • 著者名/発表者名: Ikeda T, et al.
  • 学会等名: ASBMR 29^<th> Annual Meeting
  • 発表場所: Hawaii, USA
  • 年月日: 2007-09-18
• [図書] OPLL -Ossification of the Posterior Longitudinal Ligament - 2nd Edition(edited by K. Yonenobu, T. Nakamura, Y. Toyama. Springer-Verlag Tokyo) (2006)
  • 著者名/発表者名: Hiroshi Kawaguchi, et al.
  • 総ページ数: 1023
• [備考]
  • URL: http://www.h.u-tokyo.ac.jp/ortho/