Molecular mechanisms of osteoarthritis regulation by Tace signaling

• Project/Area Number: 26462285
• 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: INUI Hiroshi 東京大学, 医学部附属病院, 講師 (60583119)
• Co-Investigator(Kenkyū-buntansha): 齋藤 琢 東京大学, 医学部附属病院, 講師 (30456107) ; 篠田 裕介 東京大学, 医学部附属病院, 講師 (80456110)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 整形外科学 / 関節病学 / Tace / 変形性関節症 / 関節症

Outline of Final Research Achievements

TNF-alpha converting enzyme (Tace), also known as a disintegrin and metallopeptidase domain 17 （Adam17), is a transmembrane enzyme which regulates various signaling pathways. Here, we have investigated how Tace regulates osteoarthritis development. Cell culture experiments and mouse experiments have revealed that Tace exerts catabolic effects on chondrocytes or cartilage.

Research Products

• [Journal Article] Different regulation of limb development by p63 transcript variants (2017)
  • Author(s): Kawata M, Taniguchi Y, Mori D, Yano F, Ohba S, Chung UI, Shimogori T, Mills AA, Tanaka S, Saito T
  • Journal Title: PLoS One Volume: 12 Issue: 3 Pages: e0174122-e0174122
  • DOI: 10.1371/journal.pone.0174122
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63. (2017)
  • Author(s): Taniguchi Y, Kawata M, Chang SH, Mori D, Okada K, Kobayashi H, Sugita S, Hosaka Y, Inui H, Taketomi S, Yano F, Ikeda T, Akiyama H, Mills AA, Chung UI, Tanaka S, Kawaguchi H, and Saito T*
  • Journal Title: Arthritis Rheumatol. Volume: 69 Issue: 3 Pages: 598-609
  • DOI: 10.1002/art.39976
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Twice cutting method reduces tibial cutting error in unicompartmental knee arthroplasty (2016)
  • Author(s): Inui H, Taketomi S, Yamagami R, Sanada T, Tanaka S
  • Journal Title: Knee Volume: 23 Issue: 1 Pages: 173-176
  • DOI: 10.1016/j.knee.2014.11.015
  • Peer Reviewed
• [Journal Article] Impingement of the Mobile Bearing on the Lateral Wall of the Tibial Tray in Unicompartmental Knee Arthroplasty. (2016)
  • Author(s): Inui H, Taketomi S, Yamagami R, Sanada T, Shirakawa N, Tanaka S.
  • Journal Title: J Arthroplasty Volume: 未定 Issue: 7 Pages: 1459-1464
  • DOI: 10.1016/j.arth.2015.12.047
  • Peer Reviewed
• [Journal Article] Snapping Pes Syndrome after Unicompartmental Knee Arthroplasty (2016)
  • Author(s): Inui H, Taketomi S, Yamagami R, Tahara K, Tanaka S
  • Journal Title: Knee Surg Relat Res Volume: 28 Issue: 2 Pages: 172-175
  • DOI: 10.5792/ksrr.2016.28.2.172
  • Peer Reviewed
• [Journal Article] Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. (2016)
  • Author(s): 1.Aini H, Itaka K, Fujisawa A, Uchida H, Uchida S, Fukushima S, Kataoka K, Saito T, Chung UI, Ohba S.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 18743-18743
  • DOI: 10.1038/srep18743
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability (2016)
  • Author(s): Chang SH, Yasui T, Taketomi S, Matsumoto T, Kim-Kaneyama JR, Omiya T, Hosaka Y, Inui H, Omata Y, Yamagami R, Mori D, Yano F, Chung U, Tanaka S, Saito T.
  • Journal Title: Osteoarthritis Cartilage Volume: 24 Issue: 4 Pages: 688-697
  • DOI: 10.1016/j.joca.2015.11.008
  • Peer Reviewed
• [Journal Article] Secure fixation of femoral bone plug with a suspensory button in anatomical anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft (2016)
  • Author(s): Taketomi S, Inui H, Nakamura K, Yamagami R, Tahara K, Sanada T, Masuda H, Tanaka S, Nakagawa T
  • Journal Title: Joints Volume: 3 Issue: 03 Pages: 102-108
  • DOI: 10.11138/jts/2015.3.3.102
  • Peer Reviewed / Open Access
• [Journal Article] <b>Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem </b><b>cells </b> (2015)
  • Author(s): Saito T, Yano F, Mori D, Kawata M, Hoshi K, Takato T, Masaki H, Otsu M, Eto K, Nakauchi H, Chung UI, Tanaka S
  • Journal Title: Biomedical Research Volume: 36 Issue: 3 Pages: 179-186
  • DOI: 10.2220/biomedres.36.179
  • NAID: 130005083858
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access
• [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] Genome-wide comprehensive analysis reveals critical cooperation between Smad and c-Fos in RANKL-induced osteoclastogenesis (2015)
  • Author(s): Omata Y, Yasui T, Hirose J, Izawa N, Imai Y, Matsumoto T, Masuda H, Tokuyama N, Nakamura S, Tsutsumi S, Yasuda H, Okamoto K, Takayanagi H, Hikita A, Imamura T, Matsuo K, Saito T, Kadono Y, Aburatani H, Tanaka S
  • Journal Title: J Bone Miner Res. Volume: 30 Issue: 5 Pages: 869-77
  • DOI: 10.1002/jbmr.2418
  • 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] Remnant-preserving anterior cruciate ligament reconstruction using a three-dimensional fluoroscopic navigation system. (2014)
  • Author(s): Taketomi S, et al.
  • Journal Title: Knee Surg Relat Res. Volume: 26 Issue: 3 Pages: 168-76
  • DOI: 10.5792/ksrr.2014.26.3.168
  • Peer Reviewed
• [Presentation] 過剰な力学的ストレス負荷による関節軟骨変性の分子メカニズム (2016)
  • Author(s): 齋藤琢
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-02
  • Invited
• [Presentation] Regulation of Articular Cartilage Homeostasis and Osteoarthritis Development by the NF-kappaB signaling. (2016)
  • Author(s): Taku Saito
  • Organizer: 2016 Cold Spring Harbor Asia Conference on Bone & Cartilage
  • Place of Presentation: Suzhou, China
  • Year and Date: 2016-10-26
  • Int'l Joint Research / Invited
• [Presentation] Perspective of disease-modifying osteoarthritis drugs (2016)
  • Author(s): Taku Saito
  • Organizer: 第3回アジア太平洋骨代謝学会議
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-20
  • Int'l Joint Research / Invited
• [Presentation] Different regulation of limb development by p63 transcript variants. (2016)
  • Author(s): Kawata M, Saito T, et al.
  • Organizer: Annual meeting of the Orthopaedic Research Society.
  • Place of Presentation: Orlando
  • Year and Date: 2016-03-08
  • Int'l Joint Research
• [Presentation] Different regulation of limb development by p63 transcript variants. (2015)
  • Author(s): Kawata M, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Seattle
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] Establishment of Surgical Destabilization Model of Mouse Ankle Osteoarthritis. (2015)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Annual meeting of the Orthopaedic Research Society.
  • Place of Presentation: Las vegas, USA
  • Year and Date: 2015-03-28
• [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 USA
  • Year and Date: 2014-09-15
• [Presentation] Expression and function of CCAAT/enhancer-binding protein family in chondrocytes. (2014)
  • Author(s): Okuma T, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Houston USA
  • Year and Date: 2014-09-12
• [Presentation] HIF-1α REGULATES CONFIGURATION AND MAINTENANCE OF ARTICULAR CARTILAGE THROUGH INDUCTION OF ANABOLIC FACTORS AND SUPPRESSION OF CATABOLIC FACTORS. (2014)
  • Author(s): Okada K, Saito T, et al.
  • Organizer: Annual meeting of Osteoarthritis Research Society International.
  • Place of Presentation: Paris
  • Year and Date: 2014-04-26
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.u-tokyo-ortho.jp/