Project/Area Number |
23592236
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
YUDOH Kazuo 聖マリアンナ医科大学, 医学(系)研究科(研究院), 教授 (60272928)
|
Co-Investigator(Kenkyū-buntansha) |
KARASAWA Rie 聖マリアンナ医科大学, 医学(系)研究科 (研究院), 講師 (50434410)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 変形性関節症 / 核酸損傷 / 酸化ストレス / メカニカルストレス / 核酸損傷修復酵素 / 軟骨細胞 / 核酸修復酵素 / DNA酸化損傷 / 細胞ストレス応答 / 軟骨変性 / 活性酸素 / DNA修復酵素 |
Research Abstract |
It is well known that chondrocytes produce excess amounts of reactive oxygen species (ROS) as well as proinflammatory cytokines and chemokines in response to mechanical and chemical stresses. An oxidized form of guanine, 8-oxo-7,8-dihydroxyguanine (8-oxoguanine), is a major causative lesion for mutagenesis by ROS, because it can cause a stable base pair with adenine or cytosine during DNA replication. 8-Oxoguanine DNA glycosylase (Ogg1) repairs 8-oxoguanine, one of the most abundant DNA adducts caused by oxygen free radicals. We demonstrated that depletion of cellular antioxidant, Ogg1, in osteoarthritic chondrocytes participates in the degeneration of articular cartilage in OA. Our findings suggest that Ogg1 may have a potential to protect against the catabolic factor-induced down-regulation of chondrocyte activity and apoptosis in OA.
|