Interleukin-1-Interleukin-17 Signaling Axis Induces Cartilage Destruction and Promotes Experimental Osteoarthritis

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 inflammationrelated 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.

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications

“…IL-17 alone dose-dependently increased MMP-1, -3, -13, and MCP-1 and decreased TIMP, COL2A1, and SOX9 mRNA expression in human OA chondrocytes [ 170 ]. When IL-17 was combined with low concentrations of IL-1β, the combination increased NO production and decreased GAG synthesis in a rat patellar articular cartilage explant model greater than either cytokine treatment alone.…”

Molecular mechanisms of mechanical load-induced osteoarthritis

“…IL-1β enhances nuclear factor erythroid-2 related factor 2 (Nrf2) and Heme Oxygenase-1 (HO-1) to upregulate matrix-degrading enzymes and oxidative stress [13]. IL-1β can upregulate MMP3 and MMP9 and ADAMTs by activating IL-17, thereby promoting joint inflammation and inducing chondrocyte apoptosis [14]. Ohtsuki et al [15] observed that IL-1β is also involved in upregulating Cell migration-inducing hyaluronidase 1 (CEMIP), which induces the degradation of hyaluronan in ECM.…”

Cryptotanshinone interferes with chondrocyte apoptosis in osteoarthritis by inhibiting the expression of miR‑574‑5p

“…The Von Frey test was used to measure the mechanical nociceptive threshold of mice at 0, 7, 14 and 21 days ( 19 ). Mice were placed on the test bench with a mesh bottom and adapted for 30 min.…”