Background 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. Previous studies have provided ample confirmation of the generation of ROS and the depletion of cellular antioxidants in degenerated articular cartilage. 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. These mutations are thought to be involved in the pathogenesis of a variety of diseases, including degenerative diseases.
Objectives This study identified mitochondrial Ogg1 as a pathogenic mechanism against catabolic factors in osteoarthritis (OA).
Methods 8-oxoguanine and Ogg1 expressions were investigated in human OA cartilages (n=5) and rat OA cartilages (n=8) by immunohistologic analysis. We studied whether OA-related catabolic factors (H2O2, IL-1b) influence expressions of Ogg1 and 8-oxoguanine in OA chondrocytes and analyzed the relationship between the cellular activity (productions of proteoglycan and type II collagen) and Ogg1 expression in human chondrocytes.
Results We observed the accumulation of an oxidized form of guanine, 8-oxoguanine, and down-regulation of its repair enzyme Ogg1 in OA rat and human chondrocytes. OA-related catabolic factors induced the over-expression of 8-oxoguanine and down-regulation of Ogg1 in chondrocytes. Furthermore, Ogg1 silencing using siRNA reduced chondrocyte activity and augments apoptosis in chondrocytes.
Conclusions Our study suggests that Ogg1 prevents catabolic stress-mediated chondrocyte dysfunction and apoptosis that might be associated with the maintenance of articular cartilage.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.