Extracellular Vesicles and Their Potential Significance in the Pathogenesis and Treatment of Osteoarthritis

Abstract

Osteoarthritis (OA) is a chronic joint disease characterized by inflammation, gradual destruction of articular cartilage, joint pain, and functional limitations that eventually lead to disability. Join tissues, including synovium and articular cartilage, release extracellular vesicles (EVs) that have been proposed to sustain joint homeostasis as well as to contribute to OA pathogenesis. EVs transport biologically active molecules, and OA can be characterized by altered EV counts and composition in synovial fluid. Of EV cargo, specific non-coding RNAs could have future potential as diagnostic biomarkers for early OA. EVs may contribute to the propagation of inflammation and cartilage destruction by transporting and enhancing the production of inflammatory mediators and cartilage-degrading proteinases. In addition to inducing OA-related gene expression patterns in synoviocytes and articular chondrocytes, EVs can induce anti-OA effects, including increased extracellular matrix deposition and cartilage protection. Especially mesenchymal stem cell-derived EVs can alleviate intra-articular inflammation and relieve OA pain. In addition, surgically- or chemically-induced cartilage defects have been repaired with EV therapies in animal models. While human clinical trials are still in the future, the potential of actual cures to OA by EV products is very promising.

Keywords: arthritis; cartilage degradation; exosome; extracellular vesicle; inflammation; mesenchymal stem cell; microvesicles; osteoarthritis.

Figure 1

Schematic representation of the roles that extracellular vesicles released by synovial joint cells could hypothetically play during the development of osteoarthritis (OA) based on the literature in the present review. Red coating around EVs depicts hyaluronan. ECM = extracellular matrix, ↓ = decrease, ↑ = increase, note that the scaling of the relative sizes of the image components is not realistic.

Figure 2

A general scheme depicting the progression of osteoarthritis (OA) and its therapies. Upper half of the image: currently available therapies that eventually lead to knee replacement surgery. Lower half of the image: potential extracellular vesicle (EV)-based therapies and the possible outcome of cartilage regeneration, GAGs = glycosaminoglycans, open source images provided by: https://www.stockio.com/free-icon/healthy-icons-syringe; https://www.flaticon.com/free-icon/x-ray_2286250; https://www.pinclipart.com/downpngs/iTxJwJo_red-pill-bottle-clipart-png-download/; https://upload.wikimedia.org/wikipedia/commons/thumb/0/0a/Methylprednisolone.png/215px-Methylprednisolone.png; https://www.flaticon.com/free-icon/stick-man-running-on-a-treadmill_31417?k=1608198863143; https://uxwing.com/knee-pain-icon/ (all image sites accessed on 29 March 2021).