Global identification of glycosylation form related to pain due to intervertebral degeneration

• Project/Area Number: 18K19595
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Sudo Hideki 北海道大学, 医学研究院, 特任准教授 (30374367)
• Co-Investigator(Kenkyū-buntansha): 西村 紳一郎 北海道大学, 先端生命科学研究院, 教授 (00183898)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 椎間板 / 糖鎖 / 痛み / 椎間板変性

Outline of Final Research Achievements

Low back pain is a common debilitating condition which pathogenesis are poorly understood. We carried out an analysis of relationship between intervertebral disc degeneration and N-glycome in a sample of rabbit intervertebral disc and plasma. Using glycoblotting analysis,N-Glycan profiling was compared between normal and degenerated intervertebral disc. The specific N-glycan score was found to be significantly greater in degenarated intervertebral disc and plasm than in normal samples. These data provide a new insight into understanding the complex pathophysiology of low back pain related intervertebral disc degeneration and suggest glycan levels as a possible biomarker for injury/degeneration-related subtypes of low back pain.

Academic Significance and Societal Importance of the Research Achievements

これまでに椎間板を対象にした糖鎖研究の報告はなく、生体材料を用いた解析にも手法的限界があった。糖鎖は核酸や蛋白質と異なり増幅を行うことが不可能なため、小型動物組織などの少量の検体からは解析に必要な量を確保できないことも糖鎖研究の障害となっていた。
本研究は、N型糖鎖の改変という糖鎖医学的側面から椎間板変性に起因する痛みを明らかにしようとする点で従来の研究とは大きく異なる。今後は椎間板変性に起因した痛みと関連する血清中のマーカーが客観的数値として捉えることが可能になれば、痛み全般に関する病態解明や治療法に関しても今後の学術の方向を変え得る新しい研究分野が創設される可能性がある。

Research Products

• [Journal Article] Effects of Intradiscal Injection of Local Anesthetics on Intervertebral Disc Degeneration in Rabbit Degenerated Intervertebral Disc (2019)
  • Author(s): Ura K, Sudo H, Iwasaki K, Tsujimoto T, Ukeba D, Iwasaki N
  • Journal Title: J Orthop Res Volume: 37 Issue: 9 Pages: 1963-1971
  • DOI: 10.1002/jor.24347
  • Peer Reviewed
• [Journal Article] Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging (2019)
  • Author(s): Ohnishi T, Yamada K, Iwasaki K, Tsujimoto T, Higashi H, Kimura T, Iwasaki N, Sudo H
  • Journal Title: Sci Rep Volume: 9 Issue: 1 Pages: 19324-19324
  • DOI: 10.1038/s41598-019-55709-3
  • Peer Reviewed / Open Access
• [Presentation] Is Discoblock Safe for Degenerated Intervertebral Discs? (2019)
  • Author(s): Katsuro Ura, Hideki Sudo, Daisuke Ukeba, Norimasa Iwasaki
  • Organizer: Orthopaedic Reseaerch Society
  • Int'l Joint Research
• [Presentation] The Role of the Caspase-3 Gene in Intervertebral Disc Degeneration Due to Injury and Aging: Analyses of Mechanisms (2019)
  • Author(s): Takashi Ohnishi, Hideki Sudo, Koji Iwasaki, Takeru Tsujimoto, Norimasa Iwasaki
  • Organizer: Orthopaedic Reseaerch Society
  • Int'l Joint Research