The dual character of exosomes in osteoarthritis: Antagonists and therapeutic agents

Exosomes have gained increasing attention as they participate in cell cross-talk in pathological environments and are functional paracrine factors of therapeutic stem cells. Osteoarthritis (OA) is a common age-related degenerative joint disease, leading to a debilitating lifestyle for sufferers. However, currently no drugs on the market promote cartilage repair, and the patients usually have to undergo arthroplasty in the late stage of OA. Although significant progress has been made in the development of stem cells for the treatment of OA and cartilage injury, problems like immune rejection remain. Recently, increasing evidence has demonstrated that exosomes from the joint microenvironment ("negative" exosomes) could play vital and complicated roles in the progression of OA. Moreover, exosomes from therapeutic cells ("therapeutic" exosomes) have also shown enormous potential for OA therapy/cartilage repair. Here, we first discuss the definition and biological background of exosomes. Then, we critically examine the roles of the "negative" exosomes in OA-affected joint. Then, we will cover the potential of the "therapeutic" exosomes for OA therapy/cartilage repair. Next, the recent progress of tissue engineering with exosomes, especially for OA therapy/cartilage repair, will also be discussed. Finally, the limitations and opportunities of exosome-based OA therapy will be outlined. STATEMENT OF SIGNIFICANCE: As natural extracellular vesicles, exosomes participate in the intercellular communication. On the basis of biological characteristics of exosomes, exosomes have their two sides for osteoarthritis (OA). On the one hand, exosomes in the OA microenvironment are involved in pathology of OA. On the other hand, exosomes from therapeutic cells have the potential as advanced strategies for OA therapy. In addition, the development of tissue engineering technology is beneficial to the exosome-based OA therapy. According to the latest research status, exosomes are of great significance and interest for the personalized and precision treatment of OA in the future, despite the limitations and challenges.