Abstract

In recent decades, the role of microRNAs (miRNAs) in human diseases has been widely studied. This research is designed to explore the effect of miR-218-5p on knee osteoarthritis (KOA) progression in a rat model with the involvement of sclerostin (SOST). The KOA rat models were constructed by Hulth method, and then were classified into the KOA, miR-218-5p inhibitor, inhibitor negative control (NC), overexpressed (OE)-SOST, OE-NC, miR-218-5p inhibitor + si-SOST, or miR-218-5p inhibitor + si-NC group. The pathological changes of rats' synovial tissues were observed; the apoptosis in rat synovial tissues was assessed; levels of IL-1β, TNF-α, PGE2 and COX-2 in serum and synovial tissues, along with SOD and MDA contents in synovial tissues were determined. The morphological changes in cartilage tissues were observed. MMP-13 and Col II expression in cartilage tissues was assessed; expression of β-catenin and Col2A1 in cartilage tissues was assessed. miR-218-5p and SOST expression in rat knee joint tissues was assessed. KOA rats had increased miR-218-5p expression and decreased SOST expression. MiR-218-5p targeted SOST. Rats injected with miR-218-5p inhibitor and OE-SOST had alleviated pathological changes, reduced TUNEL positive cell rate, decreased serum contents of IL-1β, TNF-α, PGE2, COX-2 and MDA, and increased SOD activity in synovial tissues, alleviated pathological changes, enhanced Col II positive rate and reduced MMP-13 positive rate, decreased β-catenin expression and increased Col2A1 expression in cartilage tissues. The miR-218-5p inhibition could attenuate synovial inflammation and cartilage injury in KOA rats by promoting SOST, which may be helpful for KOA treatment.

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