The integrated study for molecular backgrounds and therapeutic targets of osteoarthritis : The ROAD project.

2011 Fiscal Year Final Research Report

• Project/Area Number: 19109007
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: 国立障害者リハビリテーションセンター(研究所) (2011); The University of Tokyo (2007-2010)
• Principal Investigator: NAKAMURA Kozo 国立障害者リハビリテーションセンター(研究所), 自立支援局, 自立支援局長(研究所併任) (60126133)
• Co-Investigator(Kenkyū-buntansha): KAWAGUCHI Hiroshi 東京大学, 医学部・附属病院, 准教授 (40282660) ; TANAKA Sakae 東京大学, 医学部・附属病院, 教授 (50282661) ; AKUNE Toru 東京大学, 医学部・附属病院, 特任准教授 (60282662) ; OKA Hiroyuki 東京大学, 医学部・附属病院, 特任助教 (60401064) ; SAITO Taku 東京大学, 医学部・附属病院, 特任准教授 (30456107) ; HIROTA Jinso 東京大学, 医学部・附属病院, 助教 (30570733) ; IKEDA Toshiyuki 東京大学, 医学部・附属病院, 助教 (80322759) ; ONISHI Isao 東京大学, 医学部・附属病院, 講師 (70311628) ; TEI Yuichi 東京大学, 工学系・研究科, 教授 (30345053) ; MABUCHI Akihiko 東京大学, 医学部・附属病院, 客員准教授 (80312312)
• Co-Investigator(Renkei-kenkyūsha): ONISHI Isao 東京大学, 医学部・附属病院, 講師 (70311628) ; TEI Yuichi 東京大学, 工学系・研究科, 教授 (30345053) ; MABUCHI Akihiko 東京大学, 医学部・附属病院, 客員准教授 (80312312)
• Project Period (FY): 2007 – 2011
• Keywords: 変形性関節症 / 軟骨代謝 / 遺伝子 / 画像解析 / 疫学

Research Abstract

Social needs for prevention and treatment of osteoarthritis(OA) is increasing. We have established the ROAD project as a comprehensive study of OA for elucidation of the etiology and identification of the molecular target of treatment. Here we performed 1) cloning of regulatory molecules of cartilage degradation and elucidation of the underlying mechanism, 2) Development of measurement of the OA severity, 3) Comprehensive and systemic search for the genetic and environmental factors.

Research Products

• [Journal Article] Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice (2012)
  • Author(s): Fukai A, Kamekura S, Chikazu D, Nakagawa T, Hirata M, Saito T, Hosaka Y, Ikeda T, Nakamura K, Chung UI, and Kawaguchi H
  • Journal Title: Arthritis Rheum-US Volume: 64 Pages: 198-203
  • Peer Reviewed
• [Journal Article] C/EBP-βand RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2αas the inducer in chondrocytes (2012)
  • Author(s): Hirata M, Kugimiya F, Fukai A, Saito T, Yano F, Ikeda T, Mabuchi A, Sapkota BR, Akune T, Nishida N, Yoshimura N, Nakagawa T, Tokunaga K, Nakamura K, Chung UI, and Kawaguchi H
  • Journal Title: Hum Mol Genet Volume: 21 Pages: 1111-1123
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of endochondral ossification by HIF-2αduring skeletal growth and osteoarthritis development (2010)
  • 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, and Kawaguchi H
  • Journal Title: Nat Med Volume: 16 Pages: 678-686
  • Peer Reviewed
• [Journal Article] Cohort profile : Research on Osteoarthritis/Osteoporosis Against Disability study (2010)
  • Author(s): Yoshimura N, Muraki S, Oka H, Kawaguchi H, Nakamura K, and Akune T
  • Journal Title: Int J Epidemiol Volume: 39 Pages: 988-995
  • Peer Reviewed
• [Journal Article] Akt1 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 H, Yano F, Ogata N, Nakamura K, Chung UI, and Kawaguchi H
  • Journal Title: Arthritis Rheum Volume: 62 Pages: 826-836
  • Peer Reviewed
• [Journal Article] Regulation of osteoarthritis development by Wnt-β-catenin signaling through the endochondral ossification process (2009)
  • Author(s): Kawaguchi H
  • Journal Title: J Bone Miner Res Volume: 24 Pages: 8-11
  • Peer Reviewed
• [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, and Kawaguchi H
  • Journal Title: Arthritis Rheum Volume: 60 Pages: 166-178
  • Peer Reviewed
• [Journal Article] C/EBPβpromotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57^<Kip2> (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, and Kawaguchi H
  • Journal Title: PLoS ONE Volume: 4 Pages: e4543
  • Peer Reviewed
• [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, and Yoshimura N
  • Journal Title: Arthritis Rheum Volume: 61 Pages: 779-786
  • Peer Reviewed
• [Journal Article] Prevalence of radiographic lumbar spondylosis and its association with low back pain in the elderly of population-based cohorts : the ROAD study (2009)
  • Author(s): Muraki S, Oka H, Mabuchi A, Akune T, En-yo Y, Yoshida M, Saika A, Suzuki T, Yoshida H, Ishibashi H, Yamamoto S, Nakamura K, Kawaguchi H, and Yoshimura N
  • Journal Title: Ann Rheum Dis Volume: 68 Pages: 1401-1406
  • Peer Reviewed
• [Journal Article] Endochondral ossification signals in cartilage degradation during osteoarthritis progression in experimental mouse models (2008)
  • Author(s): Kawaguchi H
  • Journal Title: Mol Cells Volume: 25 Pages: 1-6
  • Peer Reviewed
• [Presentation] Overview of molecular backgrounds of osteoarthritis (2011)
  • Author(s): Kawaguchi H
  • Organizer: The 3rd International Cartilage and Osteoar thritis Symposium(ICOA 2011)
  • Place of Presentation: Suwon, Korea
  • Year and Date: 2011-07-05
• [Presentation] Endochondral ossification signals as potential therapeutic targets for osteoarthritis(Invited Lecture) (2011)
  • Author(s): Kawaguchi H
  • Organizer: 2011 Gordon Research Conference : Cartilage Biology & Pathology
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2011-03-08
• [Presentation] Transcriptional induction of ADAMTS5 by NF-kΒfamily member RelA/p65 in chondrocytes during osteoarthritis development (2011)
  • Author(s): Kobayashi H
  • Organizer: 2011 Gordon Research Conference : Cartilage Biology & Pathology
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2011-03-08
• [Presentation] C/EBP-βand RUNX2 in chondrocytes control cartilage degradation (2011)
  • Author(s): Hirata M
  • Organizer: 2011 Gordon Research Conference : Cartilage Biology & Pathology
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2011-03-07
• [Presentation] Notch/Rbpj/Hes1 signaling in chondrocytes controls terminal stage of endochondral ossification in skeletal growth and osteoarthritis development (2011)
  • Author(s): Sugita S
  • Organizer: 2011 Gordon Research Conference : Cartilage Biology & Pathology
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2011-03-06
• [Book] 変形性関節症の分子メカニズム-治療標的分子の同定を目指して-医学の歩み (2011)
  • Author(s): 川口浩
  • Total Pages: 531-534
• [Remarks]
  • URL: http://www.u-tokyo-ortho.jp/
• [Patent(Industrial Property Rights)] 膝関節診断支援方法及び装置並びにプログラム (2012)
  • Inventor(s): 岡敬之、吉村典子、川口浩、中村耕三
  • Industrial Property Rights Holder: 岡敬之、吉村典子、川口浩、中村耕三
  • Industrial Property Number: 特許、特許第4934786号
  • Acquisition Date: 2012-03-02
• [Patent(Industrial Property Rights)] 脊椎疾患診断支援装置、及び脊椎疾患診断支援プログラム (2010)
  • Inventor(s): 岡敬之、吉村典子、阿久根徹、川口浩、中村耕三
  • Industrial Property Rights Holder: 岡敬之、吉村典子、阿久根徹、川口浩、中村耕三
  • Industrial Property Number: 特許、特許2010-096330
  • Filing Date: 2010-04-19