Abstract
Osteoarthritis (OA) is associated with increased levels of reactive oxygen species. This study investigated if increased oxidative DNA damage accumulates in OA articular cartilage compared with nonβOA articular cartilage from pigs with spontaneous OA. Additionally, the ability of nitric oxide (NO) or peroxynitrite (ONOO^β^) induced DNA damage in nonβOA chondrocytes to undergo endogenous repair was investigated. Porcine femoral condyles were graded for the stage of OA, macroscopically by the Collins Scale, and histologically by the modified Mankin Grade. Levels of DNA damage were determined in nonβOA and OA cartilage, using the comet assay. For calibration, DNA damage was measured by exposing nonβOA chondrocytes to 0β12 Gray (Gy) of Xβray irradiation. NonβOA articular chondrocytes were treated with 0β500 Β΅M of NO donors (NOCβ18 or SINβ1), and DNA damage assessed after treatment and 5 days recovery. A significant increase (Pβ<β0.01) in oxidative DNA damage occurred in OA chondrocytes in joints with Mankin Grades 3 or greater, compared to nonβOA chondrocytes. The percentage of nuclei containing DNA damage increased significantly (Pβ<β0.001) from early to late grades of OA. An increase of approximately 0.65β1.7 breaks/1,000 kb of DNA occurred in OA, compared to nonβOA nuclei. NOCβ18 or SINβ1 caused significant DNA damage (Pβ<β0.001) in nonβOA chondrocytes that did not undergo full endogenous repair after 5 days (Pβ<β0.05). Our data suggest significant levels of oxidative DNA damage occur in OA chondrocytes that accumulates with OA progression. Additionally, DNA damage induced by NO and ONOO^β^ in nonβOA chondrocytes does not undergo full endogenous repair. J. Cell. Physiol. 217: 828β833, 2008. Β© 2008 WileyβLiss, Inc.