The Involvement of MicroRNAs in Osteoarthritis and Recent Developments: A Narrative Review

Abstract

Background: Osteoarthritis (OA) is the most common chronic joint disease and it may progressively cause disability and compromise quality of life. Lately, the role of miRNAs in the pathogenesis of OA has drawn a lot of attention. miRNAs are small, single-stranded, non-coding molecules of RNA which regulate gene expression at post-transcriptional level. The dysregulation of the expression of several miRNAs affects pathways involved in OA pathogenesis.

Objective: The purpose of this article is to review the literature on the involvement of miRNAs in the pathogenesis of OA and the implications on its diagnosis and treatment.

Materials and methods: An extensive electronic literature search was conducted by two researchers from January 2008 to August 2017. Titles and abstracts of papers were screened by the authors for further inclusion in the present work. Finally, full texts of the selected articles were retrieved.

Results: Abnormally expressed miRNAs enhance the production of cartilage degrading enzymes, inhibit the expression of cartilage matrix components, increase the production of proinflammatory cytokines, facilitate chondrocyte apoptosis, suppress autophagy in chondrocytes and are involved in pain-related pathways. miRNAs are also incorporated in extra-cellular membranous vesicles such as exosomes and participate in the intercellular communication in osteoarthritic joints.

Conclusion: Ongoing research on miRNAs has potential implications in the diagnosis and treatment of OA. Their different levels in peripheral blood and synovial fluid between OA patients and healthy population makes them candidates for being used as biomarkers of the disease, while targeting miRNAs may be a novel therapeutic strategy in OA.

Keywords: dysregulation; epigenetics; miRNAs; osteoarthritis.

Figure 1.

The synthesis of miRNAs and their mechanism of action (adjusted from Miao et al. 2013) (Miao, Yang et al. 2013). Figure 1 has been redesigned and created from scratch based on the work of Miao et al. 2013, using the Microsoft Office ® PowerPoint software.

Figure 2.

Schematic representation of basic miRNAs and their target genes. It is interesting that similar miRNAs could manifest a stimulatory as well as an inhibitory role in OA. Depending on their expression levels miRNAs play a respective role, either as OA stimulatory or OA inhibitory factors. In the lower sub-figure, the basic interactions are presented between miRNAs and their target genes (Legend: in the upper sub-figure, green arrows indicate up-regulation and red arrows indicate down-regulation. In the lower sub-figure, green arrows indicate stimulation or activation and red arrows indicate inhibition).