2023 Fiscal Year Final Research Report
Kruppel-like factor 15 deficiency exacerbates osteoarthritis through reduced expression of peroxisome proliferator-activated receptor gamma signaling in mice
| Project/Area Number |
21K09278
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
橋本 慎吾 神戸大学, 医学研究科, 特命助教 (20457089)
中野 直樹 神戸大学, 医学部附属病院, 特命助教 (40884458)
松本 知之 神戸大学, 医学研究科, 准教授 (50546588)
黒田 雄一 神戸大学, 医学部附属病院, 医員 (90884461)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | KLF-15 |
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| Outline of Final Research Achievements |
Introduction: We aimed to investigate the function of KLF15 in osteoarthritis progression.
Result: Our results indicated that KLF15 KO DMM mice exhibited significant cartilage degradation compared with WT mice. Immunohistochemistry results revealed KLF15 KO mice susceptibility to OA changes accompanied by reduced PPARγ expression. KLF15 KO DMM mice exhibited enhanced pIKKα/β, ADAMTS5 and MMP13 expression through IL-1β-induced NF-kB signaling. Furthermore, KLF15 KO mice exhibited induced chondrocyte apoptosis through reduced FOXO1 and LC3B expression.Conclusion: Our results indicated that KLF15 KO DMM mice were susceptible to alterations in OA phenotype through PPARγ signaling, including enhanced pIKKα/β, ADAMTS5 and MMP13 expression induced chondrocyte apoptosis through reduced FOXO1 and LC3B expression, suggesting that KLF15 regulation may constitute a possible therapeutic strategy for OA treatment.
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| Free Research Field |
軟骨代謝
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| Academic Significance and Societal Importance of the Research Achievements |
変形性関節症に対する新規治療薬の開発で現在のところ効果的な治療法は無い。我々は炎症の制御という観点から変形性関節症の治療法解明に現在までアプローチしてきた。KLF-15が炎症、アポトーシスを制御することは過去の報告で散見されるが、骨も含めて整形外科的領域のin vivo研究は皆無である。よってこの変形性関節症におけるKLF-15の抗炎症作用、抗アポトーシス作用に着目した本研究は非常に独創的であり意義がある。将来KLF-15の発現調節により新たな変形性関節症治療の一つになる可能性を探索する研究であり社会的な意義があると考える。
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