Exosomes for therapeutic potential in osteoarthritis

Review Article – Exosomes: roles and therapeutic potential in osteoarthritis

Abstract
Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis (OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling. This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.

Introduction
Osteoarthritis (OA) is a highly prevalent type of degenerative joint disease that affects over 300 million people worldwide.1 Chronic pain and motion dysfunction induced by OA seriously reduced the quality of life of patients. In addition, the socioeconomic burden of OA on patients and society is considerable. Current OA management is broadly divided into nonpharmacological, pharmacological, and surgical treatments.2–4 Nonpharmacological treatments, such as exercise, weight loss, and physical therapy, are suggested as the appropriate therapy for early-stage OA patients. Pharmacological treatments are mainly aimed at achieving pain control for better function and quality of daily life. Surgical treatment is most widely used for end-stage patients with serious functional disability. At present, there are few satisfactory strategies to improve joint homeostasis and delay OA progression.3,5 Understanding the underlying mechanisms of OA can facilitate the development of novel therapies for future clinical needs.
OA has been previously described primarily in terms of articular cartilage destruction, but accumulating evidence has revealed that OA is a disease with whole-joint damage and dysfunction.6,7 During OA progression, the pathologic changes in joints include cartilage damage, remodeling of the subchondral bone, inflammatory
activation in the synovium, degeneration of ligaments and the menisci, and changes in the joint capsule, bursa, periarticular muscles, nerves, and local fat pads. Several factors have been revealed to be associated with pathological changes in the OA joint, including aging, trauma, mechanical loading, and genetic and metabolic disorders.4,8 Moreover, the different tissues in the joint could influence each other during the course of OA, which may synergistically contribute to OA pathology and clinical symptoms.9–11 Subchondral bone is a layer of cortical bone below the articular cartilage and the underlying trabecular bone in the joint, which was recently proposed to play a significant role in OA pathogenesis. The subchondral bone could affect cartilage degeneration through mechanical changes or paracrine mediated bone-cartilage cross talk.12–14 The cytokines from synovial fibroblasts (SFB) of inflammatory cells could influence the degradation of the cartilage matrix and the formation of osteophytes by releasing proinflammatory factors such as IL-1β and bone-regulated factors including BMP-2.15 Inflammatory activation of the synovium and infrapatellar fat pad (IPFP) can
lead to the release of various proinflammatory mediators that not only cause widespread changes in the structure and function of synovial tissue but also promote articular cartilage damage and accelerate OA development.15–17 Therefore, investigating intercellular communication within and/or among different joint cells during OA development could be beneficial for understanding the pathogenesis of OA and exploring new therapeutic strategies for OA in the future. Exosomes are considered important mediators of cell–cell communication that participate in numerous physiological and pathological processes. Recently, the roles and therapeutic potential of exosomes in OA have been increasingly addressed in this field. In this review, we summarize the existing research on exosomes in OA and discuss the perspective and challenges related to exosome-based treatment for OA patients.

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