Multi-pathway protective effects of microRNAs on human chondrocytes in an in vitro model of osteoarthritis

Abstract Osteoarthritis is the most common degenerative joint disease. One of the main pathogenic factors in osteoarthritis is thought to be inflammation. Other factors associated with osteoarthritis are dysregulation of microRNAs, reduced autophagic activity, oxidative stress and altered metabolism. microRNAs are small non-coding RNAs that are powerful regulators of gene expression. miR-140-5p is considered a cartilage specific microRNA, is necessary for in vitro chondrogenesis, has anti-inflammatory properties and is downregulated in osteoarthritic cartilage. Its passenger strand, miR-140-3p, is the most highly expressed microRNA in healthy cartilage and increases during in vitro chondrogenesis. miR-146a is a well-known anti-inflammatory microRNA. Several studies have illustrated its role in osteoarthritis and autoimmune diseases. Here we show, when human chondrocytes were transfected individually with miR-140-5p, miR-140-3p or miR-146a, prior to stimulation with interleukin-1 beta and tumor factor necrosis-alpha as an inflammatory model of osteoarthritis, each of these microRNAs exhibited similar protective effects. Mass spectrometry analysis provided an insight to the altered proteome. All three microRNAs downregulated important inflammatory mediators. In addition they affected different proteins belonging to the same biological processes, suggesting an overall inhibition of inflammation and oxidative stress, enhancement of autophagy and restoration of other homeostatic cellular mechanisms including metabolism.