Systematic review of extracellular vesicle-derived microRNAs involved in organ fibrosis: implications for arthrofibrosis therapy

Abstract

Arthrofibrosis is defined as the excessive accumulation of connective tissue in and around joints, which interferes with the range of motion required for activities of daily living. Although joint stiffness can be restored by surgical interventions such as adhesion lysis, arthroscopic debridement, and capsular release, arthrofibrosis tends to redevelop in the months following the surgery. Thus, there is a critical and urgent need to develop a non-invasive, pharmacological therapy to prevent or resolve arthrofibrosis. A subclass of small extracellular vesicles called exosomes convey bioactive regulators like micro ribonucleic acids (miRNAs/miRs), which can function as anti- and pro-fibrotic agents. Currently, there is no research on miRNA-based therapeutic potentials for treating arthrofibrosis. Previous research and clinical observations on fibrosis across organ systems suggest that there are commonalities in pathogenic mechanisms that can be targeted in arthrofibrosis therapy. In this study, we collated and critically analyzed the existing literature on exosomal miRNAs in organ fibrosis to discover potential candidates for diagnosing, preventing, and/or treating arthrofibrosis. Fifty-six articles were finally selected and categorized by anti- and pro-fibrotic candidates of miRNAs. Notably, let-7, miR-26, miR-29, miR-146, miR-148/-152, miR-214, miR-223, and miR-21 emerged as prominent candidates that should be investigated further for effectiveness in arthrofibrosis therapy.