Analyses of mechano-sensing pathways in chondrocytes using cyclic hydroctatic pressure model

• Project/Area Number: 25670634
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: SAITO Taku 東京大学, 医学部附属病院, 准教授 (30456107)
• Co-Investigator(Kenkyū-buntansha): SAWADA Ryoko 東京大学, 医学部附属病院, 助教 (30648308) ; IKEDA Toshiyuki 東京大学, 医学部附属病院, 助教 (80322759)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 整形外科学 / 軟骨代謝 / 関節軟骨細胞 / メカニカルストレス / 軟骨代謝学 / 変形性関節症

Outline of Final Research Achievements

We first optimized experimental conditions to induce catabolic factors in mouse primary chondrocytes by cell stretch system, and analyzed gene expressions by microarray. We identified Gremlin1, which was induced by excessive cell stretch or by excessive hydrostatic pressure. Gremlin1 exerted catabolic effects in primary cultured chondrocytes and mouse knee joints, and its effects were mediated by NF-kB signaling pathway.

Research Products

• [Journal Article] Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2. (2015)
  • Author(s): Sugita S, Taketomi S, Saito T, et al.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 112 Issue: 10 Pages: 3080-5
  • DOI: 10.1073/pnas.1419699112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] <b>Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding pr</b><b>oteins </b> (2015)
  • Author(s): Okuma T, Hirata M, Yano F, Mori D, Kawaguchi H, Chung UI, Tanaka S, Saito T
  • Journal Title: Biomedical Research Volume: 36 Issue: 1 Pages: 21-29
  • DOI: 10.2220/biomedres.36.21
  • NAID: 130004903876
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access
• [Journal Article] Identification of SCAN domain zinc-finger gene ZNF449 as a novel factor of chondrogenesis. (2014)
  • Author(s): Okada K, Saito T, et al.
  • Journal Title: PLoS One. Volume: 9 Issue: 12 Pages: e115169-e115169
  • DOI: 10.1371/journal.pone.0115169
  • Peer Reviewed / Open Access
• [Journal Article] Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model. (2014)
  • Author(s): Yano F, Saito T, et al.
  • Journal Title: Ann Rheum Dis. Volume: 73 Issue: 11 Pages: 2062-4
  • DOI: 10.1136/annrheumdis-2014-205672
  • Peer Reviewed
• [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 Issue: 14 Pages: 10192-200
  • DOI: 10.1074/jbc.m113.524090
  • Peer Reviewed / Open Access
• [Journal Article] Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity. (2014)
  • Author(s): Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, Kurokawa M.
  • Journal Title: J Clin Invest. Volume: 124 Pages: 528-42
  • Peer Reviewed
• [Journal Article] Generation of Col2a1-EGFP iPS cells for monitoring chondrogenic differentiation (2013)
  • Author(s): Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
  • Journal Title: PLoS One Volume: 16;8(9) Issue: 9 Pages: e74137-e74137
  • DOI: 10.1371/journal.pone.0074137
  • Peer Reviewed
• [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] Cell-sheet technology combined with a thienoindazole derivative small compound TD-198946 for cartilage regeneration (2013)
  • Author(s): Yano F, Hojo H, Ohba S, Saito T, Honnami M, Mochizuki M, Takato T, Kawaguchi H, Chung UI.
  • Journal Title: Biomaterials. Volume: 34 Pages: 5581-7
  • Peer Reviewed
• [Presentation] Identification of Grem1 as a catabolic factor induced by mechanical stress loading in articular chondrocyte. (2014)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Houston
  • Year and Date: 2014-09-15
• [Presentation] Identification of Grem1 as a catabolic factor induced by mechanical stress loading in articular chondrocyte. (2014)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Annual meeting of Osteoarthritis Research Society International.
  • Place of Presentation: Paris
  • Year and Date: 2014-04-25
• [Presentation] IDENTIFICATION OF GREMLIN1 AS A CATABOLIC FACTOR INDUCED BY MECHANICAL STRESS LOADING IN ARTICULAR CHONDROCYTES (2014)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Osteoarthritis Research Society International
  • Place of Presentation: Paris, France
• [Presentation] Gremlin1は力学的負荷により誘導され、関節軟骨にcatabolicに作用する (2014)
  • Author(s): 張成虎、齋藤琢ほか
  • Organizer: 日本軟骨代謝学会
  • Place of Presentation: 京都
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.u-tokyo-ortho.jp/