Degenerative joint disease, a part of the process and syndrome of osteoarthritis (OA), is the most prevalent degenerative joint disease worldwide. This study aimed to examine effects of miR-23a/b-3p on degenerative joint disease. A mouse model of degenerative joint disease (officially defined as OA animal model) was established by removing the medial meniscus and anterior cruciate ligaments of the right knee. These animals were treated with miR-23a-3p mimic, miR-23b-3p mimic, miR-23a-3p inhibitor, miR-23b-3p inhibitor and their controls to determine their effects on degenerative joint disease. Expression of Grem1, miR-23a/b-3p and their downstream mediators were determined by RT-qPCR and Western blotting. Binding relationship between miR-23a/b-3p and Grem1 was determined by adopting dual luciferase reporter gene assay. Levels of inflammatory factors were determined by ELISA methods. According to the microarray data, Grem1 was a downregulated gene in degenerative joint disease. Furthermore, miR-23a/b-3p regulated Grem1 based on Web-available databases. In consistent with this, we determined increased miR-23a/b-3p expression and decreased Grem1 expression in patients and mice with degenerative joint disease. The levels of inflammatory factors and chondrocyte apoptosis were also increased in modeled mice. Inhibition of miR-23a/b-3p or overexpression of Grem1 could activate the TGF-β/Smad signaling pathway and attenuate degenerative joint disease progression both in vitro and in vivo. In addition, silencing Grem1 could ablate effect of miR-23a/b-3p inhibitor in degenerative joint disease. Our study shows that inhibition of miR-23a/b-3p delays progression of degenerative joint disease, thus providing an enhanced understanding of miRNA as a therapeutic target against degenerative joint disease.
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- ACC 2020The American College of Cardiology decided to cancel ACC.20/WCC due to COVID-19, which was scheduled to take place March 28-30 in Chicago. However, ACC.20/WCC Virtual Meeting continues to release cutting edge science and practice changing updates for cardiovascular professionals on demand and free through June 2020.