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AB0129 8-oxoguanine DNA glycosylase (OGG1) regulates the cellular function and survival of chondrocytes in response to catabolic stresses in osteoarthritis
  1. K. Yudoh
  1. Institute of medical Science, St. Marianna University School of Medicine, Kawasaki City, Japan

Abstract

Background 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, since it can form a stable base pair with adenine as well as with cytosine during DNA replication.8-oxoguanine DNA glycosylase (Ogg1) repairs the 8-oxoguanine, one of the most abundant DNA adducts caused by oxygen free radicals.

Objectives This study identified mitochondrial Ogg1 as a pathogenic mechanism in response to catabolic factors in osteoarthritis (OA).

Methods 8-oxoguanine and Ogg1 expressions were investigated in human OA cartilage and rat OA cartilage by immunohistologic analysis. We studied whether OA-related catabolic factors influence expression of Ogg1 or 8-oxoguanine in OA chondrocytes and analyzed the relationship among cellular function, apoptosis and Ogg1 or 8oxoguanine expression in human chondrocytes.

Results We observed the increased level of 8-oxoguanineand the decreased level of Ogg1 in OA chondrocytes in comparison with normal chondrocytes in OA rats as well as in patients with OA. We found that Ogg1 silencing using siRNA reduced chondrocyte activity and augments apoptosis in chondrocytes.

Conclusions The accumulation of an oxidized form of guanine, 8-oxoguanine, and down-regulation of its repair enzyme Ogg1 in OA chondrocytes may be involved in the pathogenesis of OA. Our study suggests that Ogg1 prevents catabolic stress-mediated chondrocyte dysfunction and apoptosis that might affect the maintenance of articular cartilage.

Disclosure of Interest None Declared

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