Role of DUSP-1 on the regulation of disc degeneration and innervation in the development of discogenic low back pain
| Project/Area Number |
16K10841
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
Endo Kenji 東京医科大学, 医学部, 准教授 (90266479)
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| Co-Investigator(Kenkyū-buntansha) |
山本 謙吾 東京医科大学, 医学部, 主任教授 (10246316)
澤地 恭昇 東京医科大学, 医学部, 助教(特任) (20571152)
鈴木 秀和 東京医科大学, 医学部, 兼任講師 (40317871)
小坂 泰一 東京医科大学, 医学部, 講師 (10328213)
西村 浩輔 東京医科大学, 医学部, 助教 (80516047)
松岡 佑嗣 東京医科大学, 医学部, 助教 (50408126)
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| Research Collaborator |
KUSAKABE Takuya
KONISHI Takamitsu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 椎間板性腰痛 / 椎間板変性 / 神経侵入 / DUSP1 / 神経成長因子 / 細胞外基質分解酵素 / 細胞内情報伝達 / DUSP-1 / 椎間板変性変性 |
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| Outline of Final Research Achievements |
Disease modifying drugs for discogenic low back pain (DLBP) have yet to be established. This study investigated the involvement of inflammatory signaling pathway by focusing on MAP kinases and their endogenous phosphatase, DUSP1 in the development of DLBP. Expression of nerve growth factor (associated with innervation) and matrix metalloproteinases (associated with disc degeneration) induced by IL-1 was enhanced in DUSP1 knocked down cells isolated from human intervertebral disc. This study sheds light on DUSP1 as a novel target molecule for the conservative treatment of DLBP.
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| Academic Significance and Societal Importance of the Research Achievements |
近年，細胞内情報伝達分子を標的とした薬剤開発が様々な疾患に適用されている．本研究ではMAP kinaseの3種類のサブタイプ(ERK, p38およびJNK)の阻害剤単独では，椎間板性腰痛の病態形成制御は困難であることを見出し，これらを包括的に制御しうるDUSP1にその可能性を見出した点は学術的意義のある研究といえる．また，椎間板性腰痛を含む腰痛症は我が国において最も有訴率の高い疾患であることから，DUSP1を調節することで椎間板性腰痛の病態制御の可能性を見出したことは，今後の新規椎間板性腰痛治療薬開発への礎となることが強く期待され，社会的意義の高い研究であると思われる．
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Report
(4 results)
Research Products
(21 results)
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[Presentation] Role of DUSP1 on the regulation of NGF and MMPs in human intervertebral disc cells2019
Author(s)
Takuya Kusakabe, Yasunobu Sawaji, Kenji Endo, Takamitsu Konishi, Asato Maekawa, Kazuma Murata, Taichiro Takamatsu, Yuji Matsuoka, Hidekazu Suzuki, Takato Aihara, Kengo Yamamoto
Organizer
The 46th International Society for the Study of the Lumbar Spine Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Role of DUSP1 on the regulation of NGF and MMPs in human intervertebral disc cells2018
Author(s)
Takuya Kusakabe, Yasunobu Sawaji, Kenji Endo, Takamitsu Konishi, Asato Maekawa, Takeshi Seki, Taichiro Takamatsu, Yuji Matsuoka, Hidekazu Suzuki, Takato Aihara, Kengo Yamamoto
Organizer
the 28th Japanese-Korean Combined Orthopaedic Symposium
Related Report
Int'l Joint Research
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