| Project/Area Number |
18K16613
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | University of Toyama |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 椎間板変性 / c-Fos / 疼痛 / 黄色靭帯肥厚 / 変形性脊椎症 |
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| Outline of Final Research Achievements |
Spondylosis is a common disease causes low back pain and spinal canal stenosis, and therefore, a radical treatment is required. We focused on the transcription factor c-Fos, which is located upstream of the matrix-degrading enzyme, and investigated the effects of a selective inhibitor of c-Fos/AP-1 (T-5224) on disc degeneration, disc-related pain and ligamentum flavum thickening. In a rat cocygeal disc puncture model, oral administration of T-5224 suppressed disc degeneration in imaging (X-ray, MRI) and histology fidings. In addition, T-5224 increased the threshold for pain in pain-related behaviour. In conclusion, it was suggested that selective c-Fos/AP-1 inhibition could prevent the progression of disc degeneration and related pain.
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| Academic Significance and Societal Importance of the Research Achievements |
変形性脊椎症は、有病率の高い腰痛症や脊柱管狭窄症を引き起こし、結果として身体活動の低下を招くため、社会的な負担は大きい。しかし、現在においては対症療法が中心であり、椎間板変性や黄色靭帯肥厚を抑制する根本的治療法はない。本研究では、選択的c-Fos/AP-1阻害が、椎間板変性の進行を抑制し、疼痛に対しても抑制的に働くことを示した。このことより、脊椎の退行変化に対する新たな治療法の一つとなり得ることを示した。
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