Comprehensive analysis of the inducer that degrades the extracellular matrix of articular cartilage

• Project/Area Number: 24659663
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: INUI Hiroshi 東京大学, 医学部附属病院, 助教 (60583119)
• Co-Investigator(Kenkyū-buntansha): ITO Hideya 東京大学, 医学部附属病院, 臨床登録医 (30436464) ; TAKETOMI Shuji 東京大学, 医学部附属病院, 助教 (70570018)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 関節病学

Research Abstract

We identified transcription factor that induce ADAMTS5, a crucial proteinase for osteoarthritis development by promotor analysis. The endogenous Adamts5 expression in primary chondrocyte derived from knockout mouse of this gene was decreased. In the ex vivo culture of femoral head cartilage from mesenchymal cell-specific knockout of this gene, aggrecanolysis was significantly lower than that in the control cartilage. Finally, we performed the experimental mouse osteoarthritis model in conditional knockout mouse, the conditional knockout of this gene resulted in the acceleration of osteoarthritis development because of the up-regulation of chondrocyte apoptosis. We will investigate moderate suppression of this gene could suppress the osteoarthritis development by using inhibitor of signals related to this gene.

Research Products

• [Journal Article] Identification of fibroblast growth factor-18 as a molecule to protect adult articular cartilage by gene expression profiling (2014)
  • Author(s): Mori Y, Saito T, Chang SH, Kobayashi H, Ladel CH, Guehring H, Chung UI, Kawaguchi H
  • Journal Title: J Biol Chem Volume: 289(14) Pages: 10192-200
• [Journal Article] Transcriptional induction of ADAMTS5 protein by nuclear factor-κB (NF-κB) family member RelA/p65 in chondrocytes during osteoarthritis development. (2013)
  • Author(s): Kobayashi H, Hirata M, Saito T, Itoh S, Chung UI, Kawaguchi H.
  • Journal Title: J Biol Chem. Volume: 288 Issue: 40 Pages: 28620-9
  • DOI: 10.1074/jbc.m113.452169
  • Peer Reviewed
• [Journal Article] Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development (2013)
  • Author(s): Hosaka Y, Saito T, Sugita S, Hikata T, Kobayashi H, Fukai A, Taniguchi Y, Hirata M, Akiyama H, Chung UI, Kawaguchi H
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110(5) Pages: 1875-80
• [Presentation] NF-κBファミリーメンバーRelA/p65は、軟骨細胞のアポトーシスを阻害することで、骨格形成と変形性関節症の進行を制御する
  • Author(s): 小林寛、平田真、伊藤祥三、斎藤琢、鄭雄一、中村耕三、川口浩
  • Organizer: 第26回日本軟骨代謝学会
• [Presentation] NF-κBファミリーメンバーRelA/p65は、軟骨細胞のアポトーシスを阻害することで、骨格形成と変形性関節症の進行を制御する
  • Author(s): 小林寛、平田真、伊藤祥三、斎藤琢、鄭雄一、中村耕三、川口浩
  • Organizer: 第28回日本整形外科学会基礎学術集会
• [Presentation] NF-κB family member Rela/p65 in chondrocytes controls skeletal growth and osteoarthritis development by inhibiting chondrocyte apoptosis
  • Author(s): Kobayashi H, Hirata M, Saito T, Itoh S, , Hosaka Y, Akiyama H, Chung UI, Kawaguchi H
  • Organizer: OARSI Young investigator award
• [Presentation] NF-κB family member Rela/p65 in chondrocytes controls skeletal growth and osteoarthritis development by inhibiting chondrocyte apoptosis
  • Author(s): Kobayashi H, Hirata M, Saito T, Itoh S, , Hosaka Y, Akiyama H, Chung UI, Kawaguchi H
  • Organizer: ASBMR Young investigator award