Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols

Abstract

Osteoarthritis (OA) is the most prevalent joint degenerative disease leading to irreversible structural and functional changes in the joint and is a major cause of disability and reduced life expectancy in ageing population. Despite the high prevalence of OA, there is no disease modifying drug available for the management of OA. Oxidative stress, a result of an imbalance between the production of reactive oxygen species (ROS) and their clearance by antioxidant defense system, is high in OA cartilage and is a major cause of chronic inflammation. Inflammatory mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are highly upregulated in OA joints and induce ROS production and expression of matrix degrading proteases leading to cartilage extracellular matrix degradation and joint dysfunction. ROS and inflammation are interdependent, each being the target of other and represent ideal target/s for the treatment of OA. Plant polyphenols possess potent antioxidant and anti-inflammatory properties and can inhibit ROS production and inflammation in chondrocytes, cartilage explants and in animal models of OA. The aim of this review is to discuss the chondroprotective effects of polyphenols and modulation of different molecular pathways associated with OA pathogenesis and limitations and future prospects of polyphenols in OA treatment.

Keywords: Chondrocytes; Inflammation; Nrf2; Osteoarthritis; Polyphenols; Redox.

Figure 1:

Schematic representation of normal and OA knee joint. The healthy joint (on left) has smooth cartilage surface with normal chondrocyte distribution and OA joint shows cartilage degeneration and subchondral bone changes.

Figure 2:

Schematic representation of the major signaling pathways activated by proinflammatory cytokines (IL-1β, TNFα and IL-6) in chondrocytes and their downstream effects. Stimulation of chondrocytes with IL-1β, TNFα and IL-6 leads to the activation of JAK/STAT, MAPK, AP1, NFκB and Wnt signaling pathways These cytokines also modulate mitochondrial function and ROS production. The activation of these pathways lead to increased expression of inflammatory molecules, matrix degrading proteases in chondrocytes.