Analyses of IKK signaling pathway in locomotive diseases

• Project/Area Number: 24592253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: MATSUBARA Takehiro 東京大学, 医学部附属病院, 講師 (40361498)
• Co-Investigator(Kenkyū-buntansha): KAWAGUCHI Hiroshi 東京大学, 医学部附属病院, 届出診療医 (40282660) ; CHIKUDA Hirotaka 東京大学, 医学部附属病院, 准教授 (30345219)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 整形外科学 / 変形性関節症 / 軟骨細胞 / NF-kBシグナル

Outline of Final Research Achievements

IKK family members were highly expressed in the mouse embryonic cartilage and articular cartilage of knee joints of osteoarthritis model mice. Rela, a transcription factor of NF-kB signaling pathway, was translocated from cytoplasm into nuculeus in accordance with cartilage degradation. For in vivo analyses, we generated tamoxifen-inducible conditional knockout mice. Notably, osteoarthritis development was enhanced in homo knockout mice, while it was suppressed in hetero knockout mice.

Research Products

• [Journal Article] Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. (2015)
  • Author(s): Kinugasa H, Matsubara T, et al.
  • Journal Title: Cancer Volume: 未定 Issue: 13 Pages: 2271-2280
  • DOI: 10.1002/cncr.29364
  • Peer Reviewed
• [Journal Article] Current state of continuous renal replacement therapy for acute kidney injury in Japanese intensive care units in 2011: analysis of a national administrative database. (2015)
  • Author(s): Iwagami M, Matsubara T, et al.
  • Journal Title: Nephrol Dial Transplant. Volume: 未定
  • Peer Reviewed
• [Journal Article] The Contributions of Emergency Physicians to Out-of-hospital Cardiopulmonary Arrest: An Analysis of the National Utstein Registry Data. (2015)
  • Author(s): Fukuda T, Matsubara T, et al.
  • Journal Title: J Emerg Med. Volume: 48 Issue: 4 Pages: e81-e92
  • DOI: 10.1016/j.jemermed.2014.09.053
  • Peer Reviewed
• [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] Evaluation of urinary tissue inhibitor of metalloproteinase-2 in acute kidney injury: a prospective observational study. (2014)
  • Author(s): Yamashita T, Matsubara T, et al.
  • Journal Title: Crit Care Volume: 未定
  • 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] 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 comnound TD-198946 for cartilage regeneration (2013)
  • Author(s): Yano F, Hojo H, et al.
  • Journal Title: Biomaterials Volume: 34 Issue: 22 Pages: 5581-5587
  • DOI: 10.1016/j.biomaterials.2013.04.008
  • Peer Reviewed
• [Journal Article] Hedgehog-Gli activators direct osteo-chondrogenic function of bone morp hogenetic protein toward osteogenesis in the perichondrium. (2013)
  • Author(s): Hojo H, et al.
  • Journal Title: J Biol Chem Volume: 288 Issue: 14 Pages: 9924-9932
  • DOI: 10.1074/jbc.m112.409342
  • Peer Reviewed
• [Journal Article] New biomarker panel of plasma neutrophil gelatinase-associated lipocalin and endotoxin activity assay for detecting sepsis in acute kidney injury. (2013)
  • Author(s): Katagiri D, Doi K, Matsubara T, et al.
  • Journal Title: J Crit Care. Volume: E-pub
  • Peer Reviewed
• [Journal Article] Health care costs related to out-of-hospital cardiopulmonary arrest in Japan. (2013)
  • Author(s): Fukuda T, Matsubara T, et al.
  • Journal Title: Resuscitation. Volume: E-pub
  • Peer Reviewed
• [Journal Article] A novel disease-modifying osteoarthritis drug candidate targeting Runx1. (2013)
  • Author(s): Yano F, Kawaguchi H, et al.
  • Journal Title: Ann Rheum Dis Volume: 72 Pages: 748-53
  • Peer Reviewed
• [Journal Article] β-catenin regulates PTH/PTHrP receptor signals and chondrocyte hypertrophy through binding to its intracellular C-terminal region (2013)
  • Author(s): Yano F, Kawaguchi H, et al.
  • Journal Title: Arthritis Rheum Volume: 65 Pages: 429-35
  • Peer Reviewed
• [Journal Article] Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development. (2013)
  • Author(s): Hosaka Y, Kawaguchi H, et al.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 110 Pages: 1875-80
  • Peer Reviewed
• [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
  • Place of Presentation: 千葉
• [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: 2013 Osteoarthritis Research Society International (OARSI) World Congress.
  • Place of Presentation: Philadelphia, USA
• [Presentation] Identification of fibroblast growth factor-18 as a molecule to protect and regenerate articular cartilage.
  • Author(s): Mori Y, Saito T, Ladel CH, Guehring H, Chung UI, Kawaguchi H
  • Organizer: 2013 Osteoarthritis Research Society International (OARSI) World Congress.
  • Place of Presentation: Philadelphia, USA
• [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 2013, American Society for Bone and Mineral Research
  • Place of Presentation: Boltimore, USA
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.u-tokyo-ortho.jp/
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.h.u-tokyo.ac.jp/ortho/