| Project/Area Number |
17K16693
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
SANADA Yohei 広島大学, 病院(医), 研究員 (50796117)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | Obesity / microRNA / Osteoarthritis / Ageing / osteoarthritis / obesity / hepatic steatosis / 変形性膝関節症 / 肥満 |
|---|
| Outline of Final Research Achievements |
This study aims to elucidate the mechanism of the knee osteoarthritis (OA) caused by obesity, focusing on the intracellular and extracellular functions of miR-26a, which is highly expressed in cartilage and liver.
The expression of miR-26a was highly expressed in cartilage tissue and decreased with the progress of OA. By inducing obesity, miR-26a KO mice exhibited the same obesity phenotype as wild-type mice, and no metabolic abnormality by miR-26 KO was observed. Furthermore, OA-like lesions such as osteophyte formation and cartilage degeneration were not observed in both mice. On the other hand, in cartilage-specific miR-26a Tg mice, cartilage degeneration was slightly suppressed under the aging condition of 18 months of age. These results suggest that miR-26a is not factor involved in systemic metabolic regulation but a directly involved in cartilage homeostasis.
|
| Academic Significance and Societal Importance of the Research Achievements |
変形性膝関節症(OA)の治療法は確立されておらず、対処療法や外科手術を選択せざるを得ないのが現状である。加齢に加え肥満は、OAの主要なリスク要因であるが分子機構や生物学的な情報が不足している。本研究で、miR-26aが従来の報告と異なり代謝調節に必須ではないこと、さらに肥満がOA発症のイニシエーターではない可能性が示された一方で、miR-26aは軟骨恒常性に直接関わる因子であることが示唆された。本研究は軟骨組織におけるmiR-26aの標的因子の同定を試みており、miR-26aの標的因子を介する遺伝子制御ネットワークの解明は、新たな治療薬候補の発見につながる重要な基盤情報となることが期待される。
|
