Abstract
Osteoarthritis (OA), which is the most common degenerative joint disorder, has been considered a non-inflammatory disease with abnormal mechanics. Interleukin (IL)-17 is a pleiotropic cytokine involved in inflammatory diseases and their production is driven by the cytokine including IL-1 and IL-23. However, little is known about the mechanism of IL-17 in the development of OA. Here, we investigated the role of IL-17 in the pathogenesis of OA using monosodium iodoacetate (MIA)-injected IL-17 and IL-1 receptor antagonist (IL-1Ra) double-deficient mice. In MIA-injected IL-1Ra KO mice, nociceptive properties, degree of cartilage damage, and the level of inflammatory factors in articular cartilage were increased compared to MIA-injected wild-type mice. Interestingly, the intestinal architecture was impaired in IL-1Ra KO mice compared to wild-type mice and the damage was further exacerbated by MIA injection. Deficiency of IL-17 reduced nociceptive properties and cartilage destruction, as well as inflammation-related factors in MIA-injected IL-1Ra KO mice compared to MIA-injected wild-type mice. Furthermore, IL-17-treated chondrocytes from OA patients showed enhanced expression of catabolic factors that are involved in the destruction of cartilage in OA. IL-17 accelerates the destruction of cartilage and small intestine via regulation of several inflammatory mediators in an OA murine model. These results suggest that IL-17 plays a critical role in the development of OA.
Highlights
Osteoarthritis (OA) is an age-related degenerative joint disorder characterized by progressive cartilage destruction, osteophyte formation, subchondral bone remodeling, and substantial functional disability and pain in the aged population [1]
The pathogenic role of IL-17 has been investigated on a model expressing abnormal level of IL-1 and IL-17 caused by IL-1 receptor antagonist (IL-1Ra) deficiency
Mankin and OARSI scores revealed significant cartilage thickness and depletion of proteoglycan in IL-1Ra KO mice injected with monosodium iodoacetate (MIA) compared to MIAinjected BALB/c mice (P < 0.001, One-way ANOVA followed by Bonferroni post hoc test)
Summary
Osteoarthritis (OA) is an age-related degenerative joint disorder characterized by progressive cartilage destruction, osteophyte formation, subchondral bone remodeling, and substantial functional disability and pain in the aged population [1]. Among these manifestations, cartilage homeostasis disorder is a hallmark of OA caused by degradation of extracellular matrix such as proteoglycan and type II collagen through the actions of matrix-degrading enzymes including. Recent findings suggest that inflammation plays a crucial role and is actively involved in the generation of joint symptoms and the progression of disease [5,6,7]. IL-1 is positively correlated with osteoarthritic changes and directly contributes to cartilage destruction by affecting the balance of catabolic and anabolic factors for cartilage [8, 11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
