Extracellular vesicles in cartilage homeostasis and osteoarthritis

Abstract

Purpose of review: Extracellular vesicles carry bioactive molecules that can be transferred between cells and tissues. The purpose of this review is to describe how extracellular vesicles regulate functions of cells in cartilage and other joint tissues. The potential application of extracellular vesicles in the treatment of osteoarthritis and as biomarkers will also be discussed.

Recent findings: Extracellular vesicles are found in synovial fluid, in articular cartilage and in the supernatants of synoviocytes and chondrocytes. Extracellular vesicles in cartilage have been proposed to be involved in cross talk between cells in joint tissues and to affect extracellular matrix turnover and inflammation. Extracellular vesicles from arthritic joints can promote abnormal gene expression and changes in cartilage extracellular matrix, including abnormal mineralization. Promising results were obtained in the therapeutic application of mesenchymal stem cell-derived extracellular vesicles for cartilage repair and experimental osteoarthritis.

Summary: Extracellular vesicles have emerged as vehicles for the exchange of bioactive signaling molecules within cartilage and between joint tissues to promote joint homeostasis and arthritis pathogenesis. As the molecular content of extracellular vesicles can be customized, they offer utility in therapeutic applications.

Figure 1. Electron microscopy of apoptotic chondrocytes, apoptotic bodies and matrix vesicles

(A) Electron micrograph of a chondrocyte from normal articular cartilage. Bar represents 2 μM. (B) Isolated matrix vesicles from normal cartilage. Bar represents 0.5 μM. (C) Electron micrograph of an apoptotic chondrocyte in cartilage treated with the NO donor SNP. The area indicated by the arrow is shown at higher magnification in (D). Bar represents 2 μM. (D) High magnification view of the area indicated by the arrow in (C). Bar represents 0.5 μM.

Figure 2. The effect of EV from IL-1β stimulated synovial fibroblasts on normal articular chondrocytes

Articular chondrocytes were treated with fresh-DMEM, exosomes from non-stimulated synovial fibroblasts (SFB) or exosomes from IL-1β stimulated SFB. The expression of OA-related genes was analyzed by real-time PCR. MMP-13 was significantly up-regulated, and ACAN was significantly down-regulated by exosomes from IL-1β stimulated SFB. **P < 0.01 versus Exo -IL. MD; fresh-DMEM with 10% FBS, Exo -IL; exosomes from non-stimulated SFB, Exo + IL; exosomes from IL-1β stimulated SFB.