Integrated research on intervertebral disc degeneration control targeting apoptotic response mechanism
| Project/Area Number |
17K16669
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 椎間板変性制御 / アポトーシス / Caspase3 / ノックアウトマウス / 医学 / 脊椎脊髄病学 / 椎間板変性 |
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| Outline of Final Research Achievements |
We analyzed caspase-3’s role in two different types of intervertebral disc (IVD) degeneration using caspase-3 knockout (Casp-3 KO) mice.
Apoptosis was suppressed in the IVD cells of Casp-3 KO mice, but cellular senescence was enhanced. Casp-3 KO delayed IVD degeneration in the injury-induced model but accelerated it in the age-induced model. Our results suggest that this is due to different pathological mechanisms of these two types of IVD degeneration.
This would explain why the Casp-3 KO was effective against injury-induced, but not age-related, IVD degeneration. Our results suggest that short-term caspase-3 inhibition could be used to treat injury-induced IVD degeneration.
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| Academic Significance and Societal Importance of the Research Achievements |
アポトーシス誘導遺伝子caspase3を抑制することで、外傷性椎間板変性の進行が遅延した一方、加齢性自然発症椎間板変性は増悪し、これらは異なる病態であることが本研究で明らかとなった。また、通常細胞死に至るべくある細胞のアポトーシスを人為的に抑制することにより細胞の腫瘍化等を引き起こすことが危惧されたが、caspase 3ノックアウトマウスの椎間板組織に腫瘍化細胞の出現は認めなかった。
本研究結果より、外傷性椎間板変性に対してcaspase 3 遺伝子の発現を一過性に抑制することは、椎間板組織変性制御として有用な治療手段となりうることが示唆された。
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Report
(4 results)
Research Products
(17 results)
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[Presentation] Clinical Patterns, Epidemiology, and Risk Factors of Multidrug-Resistant Pyogenic Spondylitis in Thoraco-Lumbar Spine.2019
Author(s)
Katsuhisa Yamada, Masahiko Takahata, Ken Nagahama, Akira Iwata, Tsutomu Endo, Takahi Onishi, Hideki Sudo, Manabu Ito, Norimasa Iwasaki
Organizer
American Academy of Orthopaedic Surgeons 2019 Annual Meeting
Related Report
Int'l Joint Research
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