Analysis of Muscle and Tendon Development and its application to Medicine

• Project/Area Number: 23249071
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ASAHARA Hiroshi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70294460)
• Co-Investigator(Kenkyū-buntansha): TAKADA Syuji 国立成育医療研究センター, システム発生・再生医学研究部, 部長 (20382856)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥47,970,000 (Direct Cost: ¥36,900,000、Indirect Cost: ¥11,070,000); Fiscal Year 2013: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2012: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2011: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
• Keywords: 筋 / 腱 / Mkx / RP58 / Mｋｘ / 関節 / 靭帯 / ラブドミオザルコーマ

Research Abstract

The research focused on the formation of muscle-tendon structure complex, which is essential for motor function. RP58, a transcription factor required in the development of muscle and Mkx, essential in normal growth of tendons and ligaments were investigated. In order for to determine the mechanism for Mkx expression, promoter/enhancer region of Mkx was localized and 3 candidate transcription factors were identified. Mkx regulated genes were also investigated and identified. RP58 is known to bind to DNMT3, a de novo DNA methyltransferase, and hence DNA methylation was analyzed genome-wide and regions of methylation activity were identified.

Research Products

• [Journal Article] FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice (2014)
  • Author(s): Takasawa K, Kashimada K, Pelosi E, Takagi M, Morio T, Asahara H, Schlessinger D, Mizutani S, Koopman P
  • Journal Title: The FASEB Journal Volume: 28 (5) Issue: 5 Pages: 2020-28
  • DOI: 10.1096/fj.13-246108
  • Peer Reviewed
• [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, Komori T, Asahara H (他10名)
  • Journal Title: PLos Genet Volume: 9(1) Issue: 1 Pages: 1003132-1003132
  • DOI: 10.1371/journal.pgen.1003132
  • NAID: 120006985752
  • Peer Reviewed
• [Journal Article] Identification of novel transcription-regulating genes expressed during murine molar development (2013)
  • Author(s): Uchibe K, Shimizu H, Yokoyama S, Kuboki T, Asahara H
  • Journal Title: DevDyn Volume: 241(7) Issue: 7 Pages: 1217-26
  • DOI: 10.1002/dvdy.23808
• [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