Compositional Variation and Functional Mechanism of Exosomes in the Articular Microenvironment in Knee Osteoarthritis

Abstract

Osteoarthritis (OA) is a major cause of disability worldwide with increasing age. Knee OA (KOA) is the most prevalent type of OA. Recently, it is considered that KOA is a whole joint disease, including articular cartilage, subchondral bone, synovium, ligaments, joint capsules, and muscles around the joint. Exosomes in knee joint are mainly secreted by articular chondrocytes and synoviocytes. They participate in cell and tissue cross-talk by carrying a complex cargo of proteins, lipids, nucleic acids, etc. Under normal conditions, exosomes maintain the microenvironmental homeostasis of the joint cavity. Under pathological conditions, the composition and function of exosomes changes, which in turn, disrupts the balance of anabolism and catabolism of articular chondrocyte and facilitates inflammatory responses, thus accelerating KOA progression. As a regenerative medicine, mesenchymal stem cells (MSCs) are promised to facilitate repair of degenerated cartilage and decelerate OA process. The therapeutic function of MSC mainly depends on MSC-derived exosomes, which can restore the homeostasis of the articular microenvironment. In the future, the specific mechanism of exosomes for OA treatment needs further elucidation, and the treatment effect of exosomes for long-term and/or severe OA needs further exploration.

Keywords: articular; exosomes; microenvironment; osteoarthritis.

Figure 1.

Schematic diagram of intra-articular injection of exosomes derived from MSC that act on articular chondrocytes, synoviocytes, osteoblasts, and maintain articular microenvironment homeostasis. The pathological changes of OA involved in cartilage degeneration, synovitis, and subchondral bone deterioration. Exosomes derived from MSC alter the component contents of synovial fluid. Red dots: exosomes in synovial fluid of OA; green dots: exosomes derived from MSC; yellow dots: exosomes of altered composition in OA after intra-articular injection of exosomes derived from MSC; down arrows: downregulation; and up arrows: upregulation. MSC: mesenchymal stem cell; OA: osteoarthritis.