Role of proinflammatory cytokines in the pathophysiology of osteoarthritis

Abstract

Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.

Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism

“…We did not find significant differences in the expression of Aggrecan , Mmp13 or Col X in miR‐146a‐deficient chondrocytes compared with WT control. However, following treatment with IL‐1β, a pro‐inflammatory cytokine that promotes catabolism in articular cartilage (Kapoor, Martel‐Pelletier, Lajeunesse, Pelletier & Fahmi, 2011), mRNA level of Mmp13 and Col X was significantly increased, while Aggrecan was decreased in miR‐146a‐deficient chondrocytes in comparison with WT chondrocytes (Figure 2g). This suggests that miR‐146a modulates chondrocyte anabolic and catabolic activities through affecting cytokine regulation of gene expression.…”

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

“…Many pro-inflammatory chemical mediators and pro-inflammatory cytokines are known to play critical roles in the pathogenesis of osteoarthritis [80]. Zerumbone has been investigated for potential curative effects in chemical-induced osteoarthritis in animal models.…”

Association analysis of two candidate polymorphisms in the Tumour Necrosis Factor-α gene with osteoarthritis in a Chinese population

“…Tumour necrosis factor (TNF)-α, a proinflammatory cytokine, plays an important role in local immune response to invading organisms by initiating a cascade of reactions that culminates into inflammatory response to eliminate the invading organisms [4]. Previous studies had found that levels of TNF-α were elevated in the synovial fluid, synovial membrane, subchondral bone and cartilage [5,6]. Therefore, TNF-α is considered to play an important role in the pathophysiology of OA [5].…”