Analysis of mechanisms underlying the differentiation of articular cartilage

• Project/Area Number: 24390348
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: ONO Takashi 東京大学, 医学部附属病院, 届出診療医 (00506248)
• Co-Investigator(Kenkyū-buntansha): OSHIMA Yasushi 東京大学, 医学部附属病院, 講師 (50570016) ; INUI Hiroshi 東京大学, 医学部附属病院, 助教 (60583119) ; 中川 匠 帝京大学, 医学部附属病院, 教授 (90338385)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 関節軟骨 / 変形性関節症 / FGF18 / レーザーマイクロダイセクション / Fgf18 / Timp1 / マイクロアレイ / 再生医療

Outline of Final Research Achievements

We identified many genes with higher expression in articular cartilage than in growth plate cartilage. Among them, Fgf18 was found to protect articular cartilage through the upregulation of Timp1, which has an inhibitory effect on matrix degrading enzymes.
In addition, we established a series of experimental methods of sampling a minute region of articular cartilage from cryosections using laser microdissection (LMD), and then analyzing the gene expression profiles with a next generation sequencer. Using these means, we examined differences in the profiles among several layers which comprise articular cartilage.

Research Products

• [Journal Article] <b>Determination of differential gene expression profiles in superficial and deeper zones of mature rat articular cartilage using RNA sequencing of laser microdissected tissue </b><b>specimens </b> (2014)
  • Author(s): Mori Y, Chung UI, Tanaka S, Saito T.
  • Journal Title: Biomedical Research Volume: 35 Issue: 4 Pages: 263-270
  • DOI: 10.2220/biomedres.35.263
  • NAID: 130004678582
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Usefulness of QuickDASH in patients with cervical laminoplasty. (2014)
  • Author(s): Nakamoto H, Oshima Y, Takeshita K, Chikuda H, Ono T, Taniguchi Y, Tanaka S.
  • Journal Title: J Orthop Sci. Volume: 19 Issue: 2 Pages: 218-222
  • DOI: 10.1007/s00776-013-0515-x
  • Peer Reviewed
• [Journal Article] Clinical outcome of anatomic double-bundle ACL reconstruction and 3D CT model-based validation of femoral socket aperture position (2013)
  • Author(s): Taketomi S, Inui H, Nakamura K, Hirota J, Sanada T, Masuda H, Takeda H, Tanaka S, Nakagawa T.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc. Volume: 22 Issue: 9 Pages: 2194
  • DOI: 10.1007/s00167-013-2663-0
  • Peer Reviewed
• [Journal Article] Iliotibial band irritation caused by the EndoButton after anatomic double-bundle anterior cruciate ligament reconstruction: Report of two cases (2013)
  • Author(s): Taketomi S, Inui H, Hirota J, Nakamura K, Sanada T, Masuda H, Tanaka S, Nakagawa T.
  • Journal Title: Knee Volume: 20 Issue: 4 Pages: 291
  • DOI: 10.1016/j.knee.2013.03.013
  • Peer Reviewed
• [Journal Article] Validity and reliability of the Japanese version of the painDETECT questionnaire: a multicenter observational study. (2013)
  • Author(s): Matsubayashi Y, Takeshita K, Sumitani M, Oshima Y, Tonosu J, Kato S, Ohya J, Oichi T, Okamoto N, Tanaka S.
  • Journal Title: PLoS One. Volume: 8 Issue: 9 Pages: e68013-e68013
  • DOI: 10.1371/journal.pone.0068013
  • Peer Reviewed
• [Journal Article] An additional reference axis improves femoral rotation alignment in image-free computer navigation assisted total knee arthroplasty (2013)
  • Author(s): Inui H, Nakagawa T, et al.
  • Journal Title: J Arthroplasty Volume: 28 Issue: 5 Pages: 766
  • DOI: 10.1016/j.arth.2013.01.030
  • Peer Reviewed
• [Journal Article] Validity, reliability and responsiveness of the Japanese version of the Neck Disability Index. (2013)
  • Author(s): Takeshita K, Oshima Y, Ono T, et al.
  • Journal Title: J Orthop Sci. Volume: 18 Issue: 1 Pages: 14-21
  • DOI: 10.1007/s00776-012-0304-y
  • Peer Reviewed
• [Journal Article] Natural course and prognostic factors in patients with mild cervical spondylotic myelopathy with increased signal intensity on T2-weighted magnetic resonance imaging. (2012)
  • Author(s): Oshima Y, Ono T, et al.
  • Journal Title: Spine. Volume: 37 Pages: 1909-13
  • NAID: 10031169863
  • Peer Reviewed
• [Presentation] FGF18は変形性関節症の発症・進行を抑制する (2013)
  • Author(s): 森芳史, 他
  • Organizer: 第12回 日本再生医療学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-03-22
• [Presentation] Identification of fibroblast growth factor-18 as a molecule to protect and regenerate articular cartilage. (2013)
  • 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: Piladelphia, USA