Mechanical Stimulation Protects Against Chondrocyte Pyroptosis Through Irisin-Induced Suppression of PI3K/Akt/NF-κB Signal Pathway in Osteoarthritis

Abstract

Irisin, a myokine secreted by muscle during physical exercise, is known to have biological activities in different cell types. Chondrocyte inflammation and pyroptosis have been shown to play important roles in osteoarthritis (OA). In this study, we investigated the effects of exercise-induced irisin during different intensities of treadmill exercise in a rat OA model and the anti-inflammatory and antipyroptosis mechanism of irisin in OA chondrocytes. Forty-eight SD rats (n = 8) were randomly assigned to control (CG), OA (OAG), OA groups under different intensities of treadmill exercise (OAL, OAM, and OAH), OAM + irisin neutralizing antibodies group (OAM + irisin (NA)). The levels of irisin and the severity of OA between groups were detected using ELISA, histology, immunohistochemistry, X-ray and computed tomography and magnetic resonance imaging. The anti-inflammatory and antipyroptosis mechanisms of irisin were investigated in vitro in OA chondrocytes preincubated with recombinant irisin (0, 5, or 10 ng/ml) for 1 h before treatment with interleukin-1β (IL-1β) for 24 h mRNA and protein expression levels were determined using quantitative reverse transcription polymerase chain reaction, and western blot analyses. Morphological changes and cell death associated with pyroptosis were examined using transmission electron microscopy, flow cytometry and immunofluorescence. Moderate-intensity treadmill exercise increased the levels of irisin, exhibiting the best therapeutic effects on OA which could be suppressed by irisin neutralizing antibodies. Irisin not only recovered the expression of collagen II and attenuated that of MMP-13 and ADAMTS-5 in IL-1β-induced OA chondrocytes by inhibiting the PI3K/Akt/NF-κB signaling pathway, but also inhibited the activity of nod-like receptor protein-3 (NLRP3)/caspase-1, thus ameliorating pyroptosis in chondrocytes. In conclusion, moderate mechanical stimulation protects against chondrocyte pyroptosis through irisin-induced suppression of PI3K/Akt/NF-κB signal pathway in osteoarthritis.

The effect of tai chi intervention on NLRP3 and its related antiviral inflammatory factors in the serum of patients with pre-diabetes

“…The data detected by ELISA suggested that Tai Chi intervention for 12 weeks could significantly reduce the concentration of the serum inflammatory factors including ROS, NF-κB, NEK7, NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-18 in patients with pre-diabetes, indicating that Tai Chi intervention could relieve vascular and systemic inflammation. Another important finding of our study is that the level of irisin in the blood of patients with pre-diabetes increased slightly after 12 weeks of Tai Chi intervention (P<0.01) (as shown in Figure 1B ), which is consistent with the study of Jia ( 42 ). Therefore, 12 weeks of Tai Chi intervention can significantly decrease the expressions of NEK7, NLRP3, ASC, Caspase-1, GSDMD, IL-1β, and IL-18, while increasing the expression of irisin in pre-diabetes.…”

Zhuifeng tougu capsules inhibit the TLR4/MyD88/NF-κB signaling pathway and alleviate knee osteoarthritis: In vitro and in vivo experiments

“…There is increasing evidence that the NF-κB family plays a central role in the pro-inflammatory stress response of chondrocytes and controls their differentiation processes ( Marcu et al, 2010 ). Many studies have effectively reduced chondrocyte apoptosis and alleviated the symptoms of OA by inhibiting the NF-κB signaling pathway, making significant progress in researching potential therapeutic drugs for OA ( Zhu et al, 2021 ; Chen et al, 2022 ; Jia et al, 2022 ; Ni et al, 2022 ; Shi et al, 2022 ).…”

Salidroside ameliorates severe acute pancreatitis-induced cell injury and pyroptosis by inactivating Akt/NF-κB and caspase-3/GSDME pathways

“…4 genes (CASP3, AKT1, HIF1A and IL10) were identified as candidate targets of Sal in both rattus norvegicus and homo sapiens. Recent studies have indicated that Akt/NF-κB and Caspase-3/GSDME pathways play a key role in regulating cell pyroptosis [ [31] , [32] , [33] , [34] ]. Western blot analysis was performed to measure the protein levels of Akt/NF-κB and Caspase-3/GSDME pathways-related genes.…”