Research of the Molecular Network Regulating Endochondral Ossification

2009 Fiscal Year Final Research Report

• Project/Area Number: 18209047
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: KAWAGUCHI Hiroshi The University of Tokyo, 医学部附属病院, 准教授 (40282660)
• Co-Investigator(Kenkyū-buntansha): CHUNG Ung-Il 東京大学, 大学院・工学系研究科, 教授 (30345053) ; NAKAMURA Kozo 東京大学, 医学部附属病院, 教授 (60126133) ; IKEDA Toshiyuki 東京大学, 医学部附属病院, 特任助教 (80322759) ; SAITO Taku 東京大学, 医学部附属病院, 特任助教 (30456107)
• Project Period (FY): 2006 – 2009
• Keywords: 骨 / 軟骨代謝学

Research Abstract

We identified a transcription factor p63 as the potent inducer of SOX6, a member of SOX family essential for chondrocyte generation and differentiation. In this study, we revealed that p63 was extensively expressed in chondrocytes, that p63 was indispensable for development of limb cartilage, and that p63 played important roles in every differentiation stages of chondrocytes.

Research Products

• [Journal Article] Aktl in murine chondrocytes controls cartilage calcification during endochondral ossification under physiologic and pathologic conditions (2010)
  • Author(s): Fukai A, Kawamura N, Saito T, Oshima Y, Ikeda T, Kugimiya F, Higashikawa A, Yano F, Ogata N, Nakamura K, Chung UI, Kawaguchi H.
  • Journal Title: Arthritis Rheum 62(3) Pages: 826-36
• [Journal Article] Mechanisms underlying catabolic and anabolic functions of parathyroid hormone on bone by combination of culture systems of mouse cells (2010)
  • Author(s): Shinoda Y, Kawaguchi H, Higashikawa A, Hirata M, Miura T, Saito T, Nakamura K, Chung UI, Ogata N.
  • Journal Title: J Cell Biochem. 109(4) Pages: 755-63
• [Journal Article] Screening of chondrogenic factors with a real-time fluorescence-monitoring cell line ATDC5-C2ER : identification of sorting nexin 19 as a novel factor (2009)
  • Author(s): Kan A, Ikeda T, Saito T, Yano F, Fukai A, Hojo H, Ogasawara T, Ogata N, Nakamura K, Chung UI, Kawaguchi H.
  • Journal Title: Arthritis Rheum. 60(11) Pages: 3314-23
• [Journal Article] Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice (2009)
  • Author(s): 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.
  • Journal Title: Endocrinology 150(11) Pages: 4823-34
• [Journal Article] C/EBPbeta Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57 (2009)
  • Author(s): 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.
  • Journal Title: PLoS One. 4(2) Pages: e4543
• [Journal Article] Identification of the core element responsive to runt-related transcription factor 2 in the promoter of human type X collagen gene (2009)
  • Author(s): 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.
  • Journal Title: Arthritis Rheum 60(1) Pages: 166-78
• [Journal Article] 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)
  • Author(s): Muraki S, Akune T, Oka H, Mabuchi A, En-Yo Y, Yoshida M, Saika A, Nakamura K, Kawaguchi H, Yoshimura N.
  • Journal Title: Arthritis Rheum 61(6) Pages: 779-86
• [Journal Article] The distinct role of the Runx proteins in chondrocyte differentiation and intervertebral disc degeneration : findings in murine models and in human disease (2008)
  • Author(s): 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.
  • Journal Title: Arthritis Rheum. 58(9) Pages: 2764-75
• [Journal Article] Kruppel-like factor 5 causes cartilage degradation through transactivation of matrix metalloproteinase 9 (2008)
  • Author(s): 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.
  • Journal Title: J Biol Chem. 283(36) Pages: 24682-9
• [Journal Article] Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes (2008)
  • Author(s): 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.
  • Journal Title: J Clin Invest. 118(7) Pages: 2506-15
• [Journal Article] Patchedl haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity (2008)
  • Author(s): 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.
  • Journal Title: Dev Cell. 14(5) Pages: 689-99
• [Journal Article] 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)
  • Author(s): Yamakawa K, Kamekura S, Kawamura N, Saegusa M, Kamei D, Murakami M, Kudo I, Uematsu S, Akira S, Chung UI, Nakamura K, Kawaguchi H.
  • Journal Title: Arthritis Rheum. 58(1) Pages: 172-83
• [Journal Article] Aktl in osteoblasts and osteoclasts controls bone remodeling (2007)
  • Author(s): 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.
  • Journal Title: PLoS One. 2(10) Pages: e1058
• [Journal Article] Continuous activation of G alpha q in osteoblasts results in osteopenia through impaired osteoblast differentiation (2007)
  • Author(s): Ogata N, Kawaguchi H, Chung UI, Roth SI, Segre GV.
  • Journal Title: J Biol Chem. 282(49) Pages: 35757-64
• [Journal Article] S100A1 and S100B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes (2007)
  • Author(s): Saito T, Ikeda T, Nakamura K, Chung UI, Kawaguchi H.
  • Journal Title: EMBO Rep. 8(5) Pages: 504-9
• [Journal Article] Identification of a potent combination of osteogenic genes for bone regeneration using embryonic stem (ES) cell-based sensor (2007)
  • Author(s): Ohba S, Ikeda T, Kugimiya F, Yano F, Lichtler AC, Nakamura K, Takato T, Kawaguchi H, Chung UI.
  • Journal Title: FASEB J. 21(8) Pages: 1777-87
• [Journal Article] Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability (2006)
  • Author(s): 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.
  • Journal Title: Arthritis Rheum. 54(8) Pages: 2462-70
• [Journal Article] Carminerin contributes to chondrocyte calcification during endochondral ossification (2006)
  • Author(s): 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.
  • Journal Title: Nat Med. 12(6) Pages: 665-70
• [Journal Article] Transcriptional regulation of endochondral ossification by HIF-2α during skeletal growth and osteoarthritis development
  • Author(s): 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.
  • Journal Title: Nat Med (in press)
• [Journal Article] GSK-3beta controls osteogenesis through regulating Runx2 activity
  • Author(s): Kugimiya F, Kawaguchi H, Ohba S, Kawamura N, Hirata M, Chikuda H, Azuma Y, Woodgett JR, Nakamura K, Chung UI.
• [Presentation] Molecular backgrounds of cartilage degeneration during os teoarthritis progression (Special Lecture : OARSI-KORS Cosponsored Symposium) (2009)
  • Author(s): Kawaguchi H
  • Organizer: The 35^<th> Annual Meeting of the Korean Orthopaedic Research Society
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-10-14
• [Presentation] Transcriptional regul ation of osteoarthritis progression (2008)
  • Author(s): Kawaguchi H
  • Organizer: The 13th Congress of the Asia Pacif is League of Associations for Rheuma tology (APLAR 2008)
  • Place of Presentation: Yokohama
  • Year and Date: 20080923-20080927
• [Presentation] p63 Plays a Centr al Role in Cartilage Development by Directly Regulating Key Genes for Ch ondrogenesis (2007)
  • Author(s): Ikeda T, et al.
  • Organizer: ASBMR 29^<th> Annual Meeting
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2007-09-18
• [Book] OPLL -Ossification of the Posterior Longitudinal Ligament - 2nd Edition(edited by K. Yonenobu, T. Nakamura, Y. Toyama. Springer-Verlag Tokyo) (2006)
  • Author(s): Hiroshi Kawaguchi, et al.
  • Total Pages: 1023
• [Remarks]
  • URL: http://www.h.u-tokyo.ac.jp/ortho/