From pathogenesis to therapy: extracellular vesicles in osteoarthritis.

Extracellular vesicles are membrane-bound nanoparticles that act as important elements in cell-cell signaling. Consisting of a cargo of proteins, lipids and nucleic acids, they carry information between secreting cells and target cells and induce a phenotypic or functional change in the latter. Thus, they play a multiplicity of roles in modulating physiological responses in healthy tissues. They are also active in a number of pathological conditions where they have an impact on disease progression. In recent years, EVs from several cell sources have been assessed to determine their utility as therapeutic agents to elicit an effective repair or regenerative response in diseased or injured tissues. In this regard, EVs are considered as a promising new biomedicine with the potential to overcome some of the challenges associated with conventional cell therapy. In the diarthrodial joint, EVs are produced by many cells, including chondrocytes, synovial fibroblasts, macrophages and leukocytes, where they play important roles in maintaining tissue homeostasis. They are also involved in the progression of osteoarthritis and other joint conditions. Recent compelling data also indicate that EVs transplanted to the OA joint may act as effective disease modifiers. This review provides an assessment of the functions of EVs in maintaining joint health by virtue of their multifaceted signaling activities. Their role as agents of OA progression is also discussed, as well as their therapeutic potential.