The role of oxidative and nitrosative stress in the pathology of osteoarthritis: Novel candidate biomarkers for quantification of degenerative changes in the knee joint

Abstract

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.

In vitro and in vivo potentialities for cartilage repair from human advanced knee osteoarthritis synovial fluid-derived mesenchymal stem cells

“…In addition, an increase in intra-articular SF volume causes a shift of local metabolism towards anaerobic glycolysis, thus contributing to the decrease of SF glucose levels [ 49 ]. Besides, synovial cavity damages correlates with fluctuating oxygen pressure in the joint, overproduction of free radical and lack of oxygen-processing enzymes and free radical scavenging molecules [ 50 , 51 ]. Moreover, SF-MSCs are exposed to abnormal physical load in biomechanically OA-compromised joints [ 52 ].…”

Icariin enhances cell survival in lipopolysaccharide‑induced synoviocytes by suppressing ferroptosis via the Xc‑/GPX4 axis

“…Synovitis, as the crucial pathological process in rheumatoid arthritis and osteoarthritis, is a vital research topic. During synovitis, oxidative stress and lipid peroxidation are all involved and are confirmed as vital contributors to the pathological progress (24)(25)(26). Moreover, oxidative stress and lipid peroxidation are two major causes for ferroptosis, which is an iron-dependent, non-apoptotic form of cell death, characterized by the intracellular accumulation of reactive oxygen species.…”

Prolidase expression in knee osteoarthritis and healthy controls

“…One possible cause of OA is oxidative stress due to levels of pro-inflammatory mediators, such as reactive oxygen species (ROS), that are elevated in this condition. [ 5 ] It is known that ROS stimulate pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor, which play an important role in cartilage matrix degradation. [ 1 ] Additionally, ROS reduce cartilage repair capacity and induce cell death in the extracellular matrix.…”