Oxidative DNA damage in osteoarthritic porcine articular cartilage
- 20 August 2008
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 217 (3), 828-833
- https://doi.org/10.1002/jcp.21562
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 non‐OA articular cartilage from pigs with spontaneous OA. Additionally, the ability of nitric oxide (NO) or peroxynitrite (ONOO−) induced DNA damage in non‐OA 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 non‐OA and OA cartilage, using the comet assay. For calibration, DNA damage was measured by exposing non‐OA chondrocytes to 0–12 Gray (Gy) of X‐ray irradiation. Non‐OA articular chondrocytes were treated with 0–500 µM of NO donors (NOC‐18 or SIN‐1), and DNA damage assessed after treatment and 5 days recovery. A significant increase (P < 0.01) in oxidative DNA damage occurred in OA chondrocytes in joints with Mankin Grades 3 or greater, compared to non‐OA chondrocytes. The percentage of nuclei containing DNA damage increased significantly (P < 0.001) from early to late grades of OA. An increase of approximately 0.65–1.7 breaks/1,000 kb of DNA occurred in OA, compared to non‐OA nuclei. NOC‐18 or SIN‐1 caused significant DNA damage (P < 0.001) in non‐OA chondrocytes that did not undergo full endogenous repair after 5 days (P < 0.05). 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− in non‐OA chondrocytes does not undergo full endogenous repair. J. Cell. Physiol. 217: 828–833, 2008.This publication has 43 references indexed in Scilit:
- Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with osteoarthritisOsteoarthritis and Cartilage, 2008
- Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part IIArthritis & Rheumatism, 2007
- Nitric Oxide and Peroxynitrite in Health and DiseasePhysiological Reviews, 2007
- The sensitivity of the alkaline comet assay in detecting DNA lesions induced by X rays, gamma rays and alpha particlesRadiation Protection Dosimetry, 2006
- Influence of oxygen tension on nitric oxide and prostaglandin E2 synthesis by bovine chondrocytesOsteoarthritis and Cartilage, 2005
- Apoptosis and cellular vitality: Issues in osteoarthritic cartilage degenerationArthritis & Rheumatism, 2002
- Mechanisms of chondrocyte apoptosisOsteoarthritis and Cartilage, 1999
- Reduction in the structural changes of experimental osteoarthritis by a nitric oxide inhibitorOsteoarthritis and Cartilage, 1999
- Nitric Oxide in ArthritisMethods, 1996
- Sulphate (35SO4) Uptake by Chondrocytes in Relation to Histological Changes in Osteo-Arthritic Human Articular CartilageAnnals Of The Rheumatic Diseases, 1960