Mir-25-3p in extracellular vesicles from fibroblast-like synoviocytes alleviates pyroptosis of chondrocytes in knee osteoarthritis.

Abstract

Knee osteoarthritis (KOA) is defined as a joint disease that occurs mostly among elderly people. Fibroblast-like synoviocytes-derived extracellular vesicles (FLS-EVs) have impacts on the treatment of OA. This study elucidated the mechanism of miR-25-3p in pyroptosis of chondrocytes in KOA. FLSs and EVs were extracted from neonatal mice; destabilization of the medial meniscus (DMM) was used to simulate KOA in mice, followed by the evaluation of cartilage damage and the contents of MMP-3 and MMP-13 in KOA mice. Lipopolysaccharide (LPS) was used to induce inflammation damage in mouse chondrocytes ATDC5, and the cell viability and the expressions of NLRP3, Cleaved-Caspase-1, GSDMD-N, IL-18, and IL-1β were examined. We found that FLS-EV treatment mitigated the knee-joint damage and symptoms of KOA mice, decreased MMP-3 and MMP-13, and inhibited pyroptosis of chondrocytes in DMM mice and LPS-induced ATD5 cells. Then, Cy3-labeled miR-25-3p in mice chondrocytes was observed and the expressions and the binding relation of miR-25-3p and cytoplasmic polyadenylation element-binding protein 1 (CPEB1) were verified. It showed that FLS-EVs carried miR-25-3p into chondrocytes, and upregulated miR-25-3p expression while inhibited CPEB1 transcription, resulting in mitigation of pyroptosis of chondrocytes, and CPEB1 overexpression reversed the inhibition of FLS-EVs on pyroptosis of chondrocytes in KOA.