Analysis of molecular mechanisms in disk formation and homeostasis

• Project/Area Number: 24659669
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HIROSHI Asahara 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70294460)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Mohawk / 椎間板 / 腱 / 靭帯

Outline of Final Research Achievements

We have identified the transcription factor Mkx, that is expressed in tendon/ligament and plays a important role in tendon formation. The Mkx is also expressed in annulus fibrosus of intervertebral disc. The aged Mkx knockout mice showed degeneration of annulus fibrosus. Tendon markers, such as SCX and TNMD were reduced by MKX knockdown in human annulus fibroblasts whereas SOX9, a master chondrogenesis regulator, was upregulated. Moreover, overexpression of Mkx in C3H10T1/2 cells promoted the expressions of tendon markers, and chondrogenesis and osteogenesis were inhibited.

Research Products

• [Journal Article] Transcription activator-like effector nuclease-mediated transduction of exogenous gene into IL2RG locus (2014)
  • Author(s): Matsubara Y, Chiba T, Kashimada K, Morio T, Takada S, Mizutani S, Asahara H
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 5043-5043
  • DOI: 10.1038/srep05043
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Mohawk homeobox transcription factor regulates the differentiation of tendons and volar plates (2014)
  • Author(s): Onizuka N, Ito Y, Inagawa M, Nakahara H, Takada S, Lotz M, Toyama Y, Asahara H
  • Journal Title: J Orthop Sci Volume: 19(1) Issue: 1 Pages: 172-80
  • DOI: 10.1007/s00776-013-0485-z
  • Peer Reviewed
• [Journal Article] Targeted gene deletion of miRNAs in mice by TALEN system. (2013)
  • Author(s): Takada S, Sato T, Ito Y, Yamashita S, Kato T, Kawasumi M, Kanai-Azuma M, Igarashi A, Kato T, Tamano M, Amahara H.
  • Journal Title: PLoS One. Volume: 8 Issue: 10 Pages: e76004-e76004
  • DOI: 10.1371/journal.pone.0076004
  • Peer Reviewed
• [Journal Article] The AERO System : a 3D-like Approach for Recording Gene Expression Patterns in the Whole Mouse Embryo (2013)
  • Author(s): Shimizu H, Kubo A, Uchibe K, Hashimoto M, Yokoyama S, Takada S, Mitsuoka K, Asahara H
  • Journal Title: PLOS One Volume: 8(10) Issue: 10 Pages: e75754-e75754
  • DOI: 10.1371/journal.pone.0075754
  • Peer Reviewed
• [Journal Article] Analysis of microRNAs expressions in chondrosarcoma (2013)
  • Author(s): Yoshitaka T, Kawai A
  • Journal Title: J Orthop Res Volume: 31(12) Issue: 12 Pages: 1992-1998
  • DOI: 10.1002/jor.22457
  • Peer Reviewed
• [Journal Article] Transcription factor mohawk and the pathogenesis of human anterior cruciate ligament degradation (2013)
  • Author(s): Nakahara H, Hasegawa A, Otabe K, Ayabe F, Matsukawa T, Onizuka N, Ito Y, Ozaki T, Lotz MK, Asahara H
  • Journal Title: Arthritis Rheum Volume: 65(8) Issue: 8 Pages: 2081-9
  • DOI: 10.1002/art.38020
  • Peer Reviewed
• [Journal Article] MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development. (2013)
  • Author(s): Watanabe T, Oyama T, Asada M, Harada D, Ito Y, Inagawa M, Suzuki Y, Sugano S, Katsube K, Karsenty G, Komori T, Kitagawa M, Asahara H.
  • Journal Title: PloS Genetics Volume: 9(1)
  • NAID: 120006985752
  • Peer Reviewed
• [Journal Article] Identification of novel transcription-regulating genes expressed during murine molar development. (2012)
  • Author(s): Uchibe K, Shimizu H, Yokoyama S, Kuboki T, Asahara H.
  • Journal Title: Developmental Dynamics Volume: 241(7) Pages: 1217-26
  • Peer Reviewed
• [Presentation] ゲノム編集技術による遺伝子治療の可能性 (2014)
  • Author(s): 浅原弘嗣
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-07-02
  • Invited