Synovial tissue-derived extracellular vesicles induce chondrocyte inflammation and degradation via NF-κB signalling...

Osteoarthritis (OA) is a whole-joint disease characterized by synovial inflammation and cartilage degeneration. However, the relationship between synovial inflammation and cartilage degeneration remains unclear. The modified Hulth's method was adopted to establish a knee OA (KOA) rabbit model. Synovial tissue was collected after 8 weeks, and synovial tissue-derived extracellular vesicles (ST-EVs) were extracted by filtration combined with size exclusion chromatography (SECF), followed by identification through transmission electron microscopy (TEM), nanoparticle tracer analysis (NTA) and Western blot (WB). The collagenase digestion method was used to extract normal rabbit chondrocytes, which were then treated with the SF-EVs to observe the effect and mechanism of SF-EVs on chondrocytes. The morphology, particle size and labelled protein marker detection confirmed that SECF successfully extract ST-EVs. The ST-EVs in the KOA state significantly inhibited chondrocyte proliferation and promoted chondrocytes apoptosis. Moreover, the ST-EVs also promoted the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and COX-2) and cartilage degradation-related enzymes (MMP13, MMP9 and ADAMTS5) in the chondrocytes. Mechanistically, the ST-EVs significantly promoted the activation of NF-κB signalling pathway in chondrocytes. Inhibition the activation of the NF-κB signalling pathway significantly rescued the expression of inflammatory cytokines and cartilage degradation-related enzymes in the ST-EVs-induced chondrocytes. In conclusion, the ST-EVs promote chondrocytes inflammation and degradation by activating the NF-κB signalling pathway, providing novel insights into the occurrence and development of OA.