Oxidative stress in secondary osteoarthritis: from cartilage destruction to clinical presentation?

Abstract

Due to an increasing life expectance, osteoarthritis (OA) is one of the most common chronic diseases. Although strong efforts have been made to regenerate degenerated joint cartilage, OA is a progressive and irreversible disease up to date. Among other factors the dysbalance between free radical burden and cellular scavenging mechanisms defined as oxidative stress is a relevant part of OA pathogenesis. Here, only little data are available about the mediation and interaction between different joint compartments. The article provides a review of the current literature regarding the influence of oxidative stress on cellular aging, senescence and apoptosis in different joint compartments (cartilage, synovial tissue and subchondral bone). Free radical exposure is known to promote cellular senescence and apoptosis. Radical oxygen species (ROS) involvement in inflammation, fibrosis control and pain nociception has been proven. The data from literature indicates a link between free radical burden and OA pathogenesis mediating local tissue reactions between the joint compartments. Hence, oxidative stress is likely not only to promote cartilage destruction but also to be involved in inflammative transformation, promoting the transition from clinically silent cartilage destruction to apparent OA. ROS induced by exogenous factors such as overload, trauma, local intraarticular lesion and consecutive synovial inflammation cause cartilage degradation. In the affected joint, free radicals mediate disease progression. The interrelationship between oxidative stress and OA etiology might provide a novel approach to the comprehension and therefore modification of disease progression and symptom control.

Keywords: free radicals; osteoarthritis; oxidative damage..

Figure 1

A major source structure of reactive oxidative molecules is the mitochondrion. The energy metabolism produces in oxidative phosphorylation ROS as side product of normal cellular metabolism. Disruption of chondrocyte respiration by nitric oxide induced inhibition of electron transport has been discussed to be centrally involved in chondrocyte functional compromise. In contrast a very recent study showed that the mitochondrion is a target of oxidative damage, mainly by NO related TNF-α and IL-1 induction damage of mitochondrial DNA. Mitochondrial damage by ROS/RNS has been addressed to be an important factor for chondrocyte functional compromise and apoptosis induction. Nitric oxide is released with several proinflammative factors by synovial cells as a result of inflammative transition. Nuclear transcription factor κB (NF- κ B), which is involved in the upregulation of several inflammatory genes, is an important factor for ROS/RNS induced inflammatory transition of synovial membrane. The figure shows in addition to mitochondrial damage by nitric oxide the directly damaging effects of ROS on nuclear DNA, intracellular structures and extracellular matrix.

Figure 2

Depicts the diagrammed hypothesized interrelationship between the clinical symptoms of osteoarthritis and oxidative dysbalance, attributed to the relevant compartments of the joint.