Analysis of transcription factors mediated by Wnt signal in intervertebral disc degeneration and search for therapeutic agents for low back pain

Research Project

Project/Area Number	17K10945
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Orthopaedic surgery
Research Institution	Tokai University
Principal Investigator	HIYAMA Akihiko 東海大学, 医学部, 講師 (00514382)
Co-Investigator(Kenkyū-buntansha)	酒井大輔東海大学, 医学部, 准教授 (10408007)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	腰痛 / 椎間板変性 / 分子学的研究 / 創薬 / Wntシグナル / ケモカイン / 炎症性サイトカイン / NGF / CCN family / CCR6 / CCL20 / ＣＣＮ　family / 腰痛の解明 / Cell signaling / Ｗｎｔシグナル / 神経栄養因子 / ＮＧＦ / 転写制御 / 腰痛治療薬
Outline of Final Research Achievements	Nerve growth factor (NGF) is reported to induce pain by inducing the expression of pain-related neurotransmitters. The purpose of this study is to analyze the expression of NGF by Wnt signal in rat intervertebral disc cells and to carry out a translation study for new drug discovery. We found that Wnt signal was not directly involved in the expression of NGF and that factors other than Wnt signal were indirectly involved in pain transmission. In addition, inflammatory cytokine in the intervertebral disc of patients with lumbar degenerative disease. It was suggested that the expression of CCL20 / CCR6, which is induced by CCL20 / CCR6, was confirmed. Therefore, it is considered that CCL20 / CCR6 may be involved in lumbar disc degeneration.
Academic Significance and Societal Importance of the Research Achievements	腰痛は直接生命を脅かすものではないが、ADLを下げるばかりでなく患者のQOL低下を招き、人的にも社会的にもその経済的損失は計り知れない。椎間板変性症の病態解明が明らかにされれば、腰痛治療の新規分子標的治療薬として世界に先駆けて報告でき、腰痛患者の社会的コストの減少につながる可能性がある。今回、椎間板変性に関与するWntシグナルにおける疼痛関連因子NGFの発現を解析したが、Wntシグナルは直接的にNGFの発現に関与せず、疼痛伝達ではWntシグナル以外の因子であるケモカインや炎症性サイトカインが間接的に関わっている可能性が示唆され、新たな疼痛治療薬のターゲット因子として考慮された。