Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Mitochondrial 8-Oxoguanine DNA Glycosylase (Ogg1) Regulates the Cellular Function and Survival of Osteoarthritic Chondrocytes in Response to Catabolic Stresses in Osteoarthritis.
Yudoh2, Kazuo, Karasawa1, Rie
During the development of osteoarthritis (OA), mechanical and chemical stresses on articular cartilage change the stable cellular activities of chondrocytes and produce excess amounts of reactive oxygen species (ROS) as well as proinflammatory cytokines and chemokines. Studies have provided ample confirmation of the generation of ROS and the depletion of cellular antioxidants in degenerated articular cartilage. 8-Oxoguanine DNA glycosylase (Ogg1) repairs 8-oxo-7,8-dihydroxyguanine (8-oxoG), one of the most abundant DNA adducts caused by oxygen free radicals. In the mitochondria, Ogg1 is thought to protect against activation of the intrinsic apoptotic pathway in response to oxidative stress by augmenting DNA repair in a variety of cells. However, it still remains unclear whether mitochondrial Ogg1 regulates the chondrocyte function and cellular survival in osteoarthritic cartilage tissue.
The aim of the study was examined the potential involvement of mitochondrial Ogg1 in the pathogenesis of OA.
Ogg1 expression was investigated in human OA cartilage and rat OA cartilage by immunohistologic analysis. We studied whether IL-1beta and H2O2 induce Ogg1 expression in OA chondrocytes and analyzed the relationship between cellular apoptosis phenotypes and Ogg1 expression in human chondrocytes.
We observed the decreased levels of Ogg1 in osteoarthritic chondrocytes in comparison with normal chondrocytes in animal models of osteoarthritis (OA) and patients with OA, suggesting the involvement of down-regulation of Ogg1 in the degeneration of articular cartilage in OA. We found that mitochondrial Ogg1 silencing using siRNA reduced chondrocyte activity and augments apoptosis in human ostearthritic chondrocytes. In the previous studies, we have focused on nanocarbon particle, fullerene (C60), which acts a strong free radical scavenger, as an anti-oxidative agent, to prevent the degeneration of articular cartilage in OA. We have demonstrated that water-soluble fullerene has a potential as a protective agent against the catabolic stress-induced degeneration of articular cartilage both in vitro and in vivo OA models. In the present study, we found that C60 fullerene increased the expressions of Ogg1 in osteoarthritic chondrocytes.
Our recent study revealed the potential involvement of accumulation of 8-Oxoguanine, an oxidized form of guanine, and impairment of mitochondrial DNA repair enzymes in the pathogenesis of OA. These findings suggest that mt-hOgg1 prevents catabolic stress-mediated chondrocyte dysfunction and apoptosis that might be important in the maintenance of articular cartilage. C60 fullerene may have a therapeutic potential, as a nanomedicine, to protect against the degeneration of articular cartilage in OA.
To cite this abstract, please use the following information:
Yudoh, Kazuo, Karasawa, Rie; Mitochondrial 8-Oxoguanine DNA Glycosylase (Ogg1) Regulates the Cellular Function and Survival of Osteoarthritic Chondrocytes in Response to Catabolic Stresses in Osteoarthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :631