Comprehensive research for molecular regulation of development, homeostasis, and degeneration of spine

• Project/Area Number: 17H04311
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Gunma University
• Principal Investigator: Chikuda Hirotaka 群馬大学, 大学院医学系研究科, 教授 (30345219)
• Co-Investigator(Kenkyū-buntansha): 田中 栄 東京大学, 医学部附属病院, 教授 (50282661) ; 大島 寧 東京大学, 医学部附属病院, 准教授 (50570016) ; 松林 嘉孝 東京大学, 医学部附属病院, 助教 (50747962)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: 脊椎 / 整形外科学 / 脊椎脊髄病学

Outline of Final Research Achievements

In the present study, we analyzed expression profiles of spinal components, including annulus fibrosus, nucleus pulposus, paraspinal ligaments, etc. by lasermicrodissection and RNA sequencing. We performed pathway analyses and identified TGF-beta signaling may play pivotal roles in develpment of spine. We further identified candidate genes expressed in the inner layer of annulus fibrosus, and developed their Cre mice.

Academic Significance and Societal Importance of the Research Achievements

変形性腰椎症は変形性膝関節症を上回る膨大な患者数がいるものの、人工膝関節置換術のような長期に安定した治療法はない。分子病態解明、さらには発生学的研究においても、脊椎は四肢関節と比べて大きく立ち遅れている。本研究によって得られた組織特異的Creマウスなどのバイオリソースや発現解析のデータベースは、脊椎疾患の研究に広く貢献するものである。

Research Products

• [Journal Article] A systematic review and meta-analysis comparing anterior decompression with fusion and posterior laminoplasty for cervical ossification of the posterior longitudinal ligament (2020)
  • Author(s): Yoshii Toshitaka、Egawa Satoru、Hirai Takashi、Kaito Takashi、Mori Kanji、Koda Masao、Chikuda Hirotaka、Hasegawa Tomohiko、Imagama Shiro、Yoshida Masahiro、Iwasaki Motoki、Okawa Atsushi、Kawaguchi Yoshiharu
  • Journal Title: Journal of Orthopaedic Science Volume: 25 Issue: 1 Pages: 58-65
  • DOI: 10.1016/j.jos.2019.03.004
  • Peer Reviewed
• [Journal Article] Lysophosphatidic acids and their substrate lysophospholipids in cerebrospinal fluid as objective biomarkers for evaluating the severity of lumbar spinal stenosis (2019)
  • Author(s): Hayakawa Kentaro、Kurano Makoto、Ohya Junichi、Oichi Takeshi、Kano Kuniyuki、Nishikawa Masako、Uranbileg Baasanjav、Kuwajima Ken、Sumitani Masahiko、Tanaka Sakae、Aoki Junken、Yatomi Yutaka、Chikuda Hirotaka
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 9144-9144
  • DOI: 10.1038/s41598-019-45742-7
  • Peer Reviewed / Open Access
• [Journal Article] Unusual Painful Muscle Spasm in a Dialysis-Dependent Patient with Progressive Cervical Kyphosis (2019)
  • Author(s): Tsunoda Daisuke、Iizuka Yoichi、Mieda Tokue、Iizuka Haku、Chikuda Hirotaka
  • Journal Title: Case Reports in Orthopedics Volume: 2019 Pages: 1-4
  • DOI: 10.1155/2019/7062568
  • Peer Reviewed
• [Journal Article] Risk Factors for Rapidly Progressive Neurological Deterioration in Cervical Spondylotic Myelopathy (2019)
  • Author(s): Takasawa Eiji、Sorimachi Yasunori、Iizuka Yoichi、Tsunoda Daisuke、Mieda Tokue、Iizuka Haku、Chikuda Hirotaka
  • Journal Title: SPINE Volume: 44 Issue: 12 Pages: E723-E730
  • DOI: 10.1097/brs.0000000000002969
  • Peer Reviewed
• [Journal Article] Oral administration of EP4-selective agonist KAG-308 suppresses mouse knee osteoarthritis development through reduction of chondrocyte hypertrophy and TNF secretion (2019)
  • Author(s): Murahashi Yasutaka、Yano Fumiko、Chijimatsu Ryota、Nakamoto Hideki、Maenohara Yuji、Amakawa Masahiro、Miyake Yoshihide、Yamanaka Hiroyuki、Iba Kousuke、Yamashita Toshihiko、Tanaka Sakae、Saito Taku
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 20329-20329
  • DOI: 10.1038/s41598-019-56861-6
  • Peer Reviewed / Open Access
• [Journal Article] The three-year efficacy of iguratimod in clinical daily practice in patients with rheumatoid arthritis (2018)
  • Author(s): Suto Takahito、Yonemoto Yukio、Okamura Koichi、Sakane Hideo、Takeuchi Kimihiko、Tamura Yasuyuki、Kaneko Tetsuya、Ayabe Keio、Chikuda Hirotaka
  • Journal Title: Modern Rheumatology Volume: Aug 10 Issue: 5 Pages: 1-7
  • DOI: 10.1080/14397595.2018.1510879
  • Peer Reviewed
• [Journal Article] Phase I clinical trial of percutaneous cryoablation for osteoid osteoma (2018)
  • Author(s): Miyazaki Masaya、Saito Kenichi、Yanagawa Takashi、Chikuda Hirotaka、Tsushima Yoshito
  • Journal Title: Japanese Journal of Radiology Volume: 36 Issue: 11 Pages: 669-675
  • DOI: 10.1007/s11604-018-0768-6
  • NAID: 50013030588
  • Peer Reviewed
• [Journal Article] Long-term patient reported outcomes of elbow, wrist and hand surgery for rheumatoid arthritis (2018)
  • Author(s): Okura Chisa、Ishikawa Hajime、Abe Asami、Yonemoto Yukio、Okamura Koichi、Suto Takahito、Oyakawa Tomo、Miyagawa Yusuke、Otani Hiroshi、Ito Satoshi、Kobayashi Daisuke、Nakazono Kiyoshi、Murasawa Akira、Takagishi Kenji、Chikuda Hirotaka
  • Journal Title: International Journal of Rheumatic Diseases Volume: 21 Issue: 9 Pages: 1701-1708
  • DOI: 10.1111/1756-185x.13340
  • Peer Reviewed
• [Journal Article] Short-term daily teriparatide in patients with rheumatoid arthritis (2017)
  • Author(s): Kaneko Tetsuya、Okamura Koichi、Yonemoto Yukio、Okura Chisa、Suto Takahito、Tachibana Masahiro、Tamura Yasuyuki、Inoue Makoto、Chikuda Hirotaka
  • Journal Title: Mod Rheumatol. Volume: 14 Issue: 3 Pages: 1-6
  • DOI: 10.1080/14397595.2017.1362093
  • Peer Reviewed
• [Journal Article] Direct evidence of central nervous system axonal damage in patients with postoperative delirium: A preliminary study of pNF-H as a promising serum biomarker (2017)
  • Author(s): Inoue Reo、Sumitani Masahiko、Ogata Toru、Chikuda Hirotaka、Matsubara Takehiro、Kato So、Shimojo Nobutake、Uchida Kanji、Yamada Yoshitsugu
  • Journal Title: Neurosci Lett. Volume: 653 Pages: 39-44
  • DOI: 10.1016/j.neulet.2017.05.023
  • Peer Reviewed
• [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] 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, and Saito T
  • Journal Title: Spine Volume: 印刷中
  • Peer Reviewed
• [Presentation] A Mouse Intervertebral Disc Degeneration Model by Surgically-induced Instability (2017)
  • Author(s): Oichi T, Saito T, et al
  • Organizer: Annual meeting of the Orthopaedic Research Society
  • Int'l Joint Research