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Multi-pathway Protective Effects of MicroRNAs on Human Chondrocytes in an In Vitro Model of Osteoarthritis.

Abstract：

:Osteoarthritis (OA) is the most common degenerative joint disease. One of the main pathogenic factors of OA is thought to be inflammation. Other factors associated with OA 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 OA and autoimmune diseases. We show that, 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 OA, 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.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Al-Modawi RN,Brinchmann JE,Karlsen TA

doi

10.1016/j.omtn.2019.07.011

subject

Has Abstract

pub_date

2019-09-06 00:00:00

pages

776-790

issn

2162-2531

pii

S2162-2531(19)30201-X

journal_volume

17

pub_type

杂志文章

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