Development of novel treatment for intervertebral disc degeneration

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09634
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Fujita Health University
• Principal Investigator: Fujita Nobuyuki 藤田医科大学, 医学部, 教授 (30348685)
• Co-Investigator(Kenkyū-buntansha): 堀内 圭輔 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 整形外科学, 准教授 (30327564)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 椎間板変性 / ヒアルロン酸 / 慢性炎症 / 髄核

Outline of Final Research Achievements

RT-PCR and Western blot analysis showed that TNF-α-mediated induction of the expression of TNF-α and COX2 was clearly neutralized by HA treatment, and the expression of TNF-α and COX2 was significantly induced by hyaluronidase treatment in both cell types. Additionally, Western blot analysis showed that hyaluronidase-induced phosphorylation of p38 and Erk1/2, and that TNF-α-mediated phosphorylation of p38 and Erk1/2 was clearly reduced by HA addition. In degenerating human IVD samples, immunohistochemistry for hyaluronidase showed that the expression of hyaluronidases including HYAL1, HYAL2, and CEMIP tended to increase in accordance with IVDD. In particular, HYAL1 showed statistically significant differences.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

腰椎変性疾患の原因の一つに椎間板変性が挙げられるが、現在のところ、椎間板変性を抑制する有効な治療法は確立されていない。本研究結果より、ヒアルロン酸がp38とErk1/2経路を制御することで、椎間板の炎症を抑制する可能性が示された。更に、HYAL1の発現が椎間板変性の進行と相関していることも示された。以上より、HYAL1がHA代謝を介して、椎間板変性の治療標的分子となる可能性が示唆された。