Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.
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.
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, QC H2L 4M1, Canada.
Mohit
M
Kapoor
Johanne
J
Martel-Pelletier
Daniel
D
Lajeunesse
Jean-Pierre
JP
Pelletier
Hassan
H
Fahmi
D002358:Cartilage, Articular / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D010003:Osteoarthritis / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha