Regulation of articular joint diseases by transcription factor family C/EBP

• Project/Area Number: 15K10462
• 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: Morizaki Yutaka 東京大学, 医学部附属病院, 助教 (30508099)
• Co-Investigator(Kenkyū-buntansha): 田中 健之 東京大学, 医学部附属病院, 助教 (00583121) ; 矢野 文子 東京大学, 医学部附属病院, 特任講師 (80529040)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 整形外科学 / 変形性関節症

Outline of Final Research Achievements

CCAAT/enhancer-binding protein (C/EBP) beta regulates chondrocyte differentiaion and proliferation during endochondral ossification. In the present study, we examined expression and function of other C/EBP family members in chondrocytes. Among
four members with transactivation domain, expression of Cebpb and Cebpd was abundant compared to Cebpa. C/EBPs suppressed expressions of early differentiation
markers including Col2a1, aggrecan and Sox9, enhanced those of late differentiation markers including Mmp13, Vegfa and Col10a1, and decelerated cell proliferation, indicating their overlapped functions in chondrocytes. In contrast, A-CEBP, which exerts a dominant-negative effect against all C/EBPs, increased expressions of early differentiation markers and decreased those of late differentiation markers.

Research Products

• [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] 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] Sandwich-type PLLA-nanosheets loaded with BMP-2 induce bone regeneration in critical-sized mouse calvarial defects (2017)
  • Author(s): Huang KC, Yano F, Murahashi Y, Takano S, Kitaura Y, Chang SH, Soma K, Ueng SWN, Tanaka S, Ishihara K, Okamura Y, Moro T, Saito T
  • Journal Title: Acta Biomater Volume: 59 Pages: 12-20
  • DOI: 10.1016/j.actbio.2017.06.041
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Mouse Intervertebral Disc Degeneration Model by Surgically-Induced Instability (2017)
  • Author(s): Oichi T, Taniguchi Y, Soma K, Chang SH, Yano F, Tanaka S, Saito T
  • Journal Title: Spine Volume: ― Issue: 10 Pages: 1-1
  • DOI: 10.1097/brs.0000000000002427
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Grey-scale sonography and sonoelastography for diagnosing carpal tunnel syndrome. (2016)
  • Author(s): Miyamoto H, Morizaki Y, Kashiyama T, Tanaka S.
  • Journal Title: World J Radiol. Volume: 8 Issue: 3 Pages: 281-7
  • DOI: 10.4329/wjr.v8.i3.281
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence of hand osteoarthritis and its relationship to hand pain and grip strength in Japan: The third survey of the ROAD study. (2016)
  • Author(s): Kodama R, Muraki S, Oka H, Iidaka T, Teraguchi M, Kagotani R, Asai Y, Yoshida M, Morizaki Y, Tanaka S, Kawaguchi H, Nakamura K, Akune T, Yoshimura N.
  • Journal Title: Mod Rheumatol Volume: 26 Issue: 5 Pages: 767-773
  • DOI: 10.3109/14397595.2015.1130673
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes. (2016)
  • Author(s): Kobayashi H, Chang S, Mori D, Itoh S, Hirata M, Hosaka Y, Taniguchi Y, Okada K, Mori Y, Yano F, Chung U, Akiyama H, Kawaguchi H, Tanaka S, Saito T.
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 13336-13336
  • DOI: 10.1038/ncomms13336
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] Prevalence of hand osteoarthritis and its relationship to hand pain and grip strength in Japan: The third survey of the ROAD study. (2016)
  • Author(s): Kodama R, Muraki S, Oka H, Iidaka T, Teraguchi M, Kagotani R, Asai Y, Yoshida M, Morizaki Y, Tanaka S, Kawaguchi H, Nakamura K, Akune T, Yoshimura N.
  • Journal Title: Mod Rheumatol. Volume: not yet
  • Peer Reviewed
• [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] Runx1 and Runx3 Are Downstream Effectors of Nanog in Promoting Osteogenic Differentiation of the Mouse Mesenchymal Cell Line C3H10T1/2 (2015)
  • Author(s): Saito T, Ohba S, Yano F, Seto I, Yonehara Y, Takato T, Ogasawara T
  • Journal Title: Cell Reprogram Volume: 17 Issue: 3 Pages: 227-234
  • DOI: 10.1089/cell.2014.0059
  • Peer Reviewed / Open Access
• [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
• [Presentation] Runx1による軟骨分化制御機構 (2016)
  • Author(s): 矢野文子、ほか
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] Runx1による軟骨分化制御機構 (2016)
  • Author(s): 矢野文子、ほか
  • Organizer: 第34回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-20
  • Invited
• [Presentation] Runx1による軟骨分化制御機構 (2015)
  • Author(s): 矢野文子、他
  • Organizer: 第16回運動器科学研究会
  • Place of Presentation: 南日本新聞 みなみホール（鹿児島県・鹿児島市）
  • Year and Date: 2015-09-12
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.u-tokyo-ortho.jp/