Temsirolimus Is a Candidate of the Optimal mTOR Inhibitor in Human Intervertebral Disc Nucleus Pulposus Cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16685
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kobe University
• Principal Investigator: Kakiuchi Yuji 神戸大学, 医学研究科, 医学研究員 (40849212)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: オートファジー / 椎間板 / mTORC1阻害

Outline of Final Research Achievements

an in-vivo study was designed to clarify effects of mTORC1 modulation by Raptor RNAi in a rat tail model of intervertebral disc degeneration induced by temporary static compression. In-vivo intradiscal RNAi knockdown of Raptor demonstrated enhanced cellular autophagy, inhibited apoptotic cell death and senescent cell aging, radiographic height loss, and histological degeneration, indicating disc cell and matrix-protective effects. On the other hand, for degenerated discs induced by prior compressive load, the effects of RNAi were relatively limited.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

本研究でラットの尾椎椎間板においてmTORC1を阻害することによりオートファジーの誘導や細胞死・細胞老化の抑制、細胞外基質分解抑制などを介して椎間板保護作用を生じる可能性が示唆された。腰痛は世界的な健康問題の一つであり、椎間板変性と深い関連がある。本研究のように椎間板内への注射による治療で椎間板変性を抑制し椎間板機能を温存できる可能性が示唆された。