Mechanism for the Chondroprotective Effects of Glycolysis Inhibitor
| Project/Area Number |
18K16678
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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 | Nagoya University (2019-2020)
National Hospital Organization Nagoya Medical Center (2018) |
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Principal Investigator |
Terabe kenya 名古屋大学, 医学部附属病院, 病院助教 (10816870)
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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 |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 変形性関節症 / metabolic reprogramming / 嫌気性解糖 / 2-Deoxy-D-glucose / 軟骨代謝 / 代謝リプログラミング / 軟骨細胞 |
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| Outline of Final Research Achievements |
We mainly demonstrated that inflammation by induced metabolic reprogramming which is reduced mitochondrial potential and enhanced dependence on glycolysis in chondrocytes.
We also demonstrated that glycolysis inhibitors such as 2DG returned the cell metabolism, and reversed the pro-inflammatory agents-induced increases the expression of MMP13. Although IL-1β lost safranin O staining in cartilage samples, coincubation with glycolysis inhibitors blocked in the loss of proteoglycan. AMPK is associate with energy homeostasis in chondrocytes. IL-1β treatment decreased accumulation of phosphor AMPK but co-treatment with glycolysis inhibitors resulted in a rescue of the pAMPK status. Co treatment with AICAR, which is inducer of AMPK, also induced chonroprotective effect, glycolysis inhibitors or AICAR have chondroprotective effect by changing metabolism and upregulate AMPK.
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| Academic Significance and Societal Importance of the Research Achievements |
OAは一般的な関節障害である一方で、これまでに臨床応用されているのは高分子ヒアルロン酸の関節内注射のみであり、変性進行を制御する薬物治療の確立には至っていない。OAはメタボリックシンドロームに共通する慢性炎症を基盤とした全身性疾患ととらえられるようになっており、この観点からも軟骨変性において代謝リプログラミングが関与していることを本研究で明らかにしたことは重要である。さらにこの代謝を制御して効果を発現する2DG、ガラクトースやAICARが軟骨保護作用を有することを明らかにしたのは画期的である。これによりOAの病因、病態理解につながるのみならず、新たなOA治療薬に発展することが期待できる。
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Report
(4 results)
Research Products
(23 results)
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[Presentation] The Metabolic Change In Osteoarthritis2021
Author(s)
Yoshifumi Ohashi,Nobunori Takahashi, Kenya Terabe, Toshihisa Kojima,Shirou lmagama, Cheryl . Knudson, Warren Knudson
Organizer
Orthopaedic Research Society 2021 Annual Meeting Registration
Related Report
Int'l Joint Research
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