Exosomes rewire the cartilage microenvironment in osteoarthritis: from intercellular communication to therapeutic strategies

Abstract

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide. However, effective strategies for cartilage repair are lacking, and patients with advanced OA usually need joint replacement. Better comprehending OA pathogenesis may lead to transformative therapeutics. Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior. Specifically, exosome cargos, such as noncoding RNAs (ncRNAs) and proteins, play a crucial role in OA progression by regulating the proliferation, apoptosis, autophagy, and inflammatory response of joint cells, rendering them promising candidates for OA monitoring and treatment. This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA, suggesting new realms to improve OA management.

A new frontier in temporomandibular joint osteoarthritis treatment: Exosome-based therapeutic strategy

“…It was shown that miR-21-5, as a lead cardioactive MSC-exosomal-microRNA, mediated effects on increasing engineered cardiac tissues contractility and was suggested as a specific molecular target for optimizing cardio-therapies (Mayourian et al, 2018). In recent years, increasing studies have been conducted on the application of exosomes in the treatment of neurological diseases (Budden et al, 2021;Xu et al, 2017;Rufino-Ramos et al, 2017). More attention should also be paid to bottlenecks in exosome treatment, including the limitation of increasing exosome production, the difficulty of analyzing the effective components of exosomes and the better improvement of the functions of the active component.…”

“…The crosstalk between the cartilage and subchondral bone is proceeding in an orderly manner, conducted in an exosome-dependent pattern (Domenis et al, 2017). Once the balance of the interaction is disrupted, cartilage breaks down and subchondral bone remodels abnormally, exacerbating the progression of OA (Wu et al, 2022). TMJ is one of the most flexible joints in the body and the subchondral bone of TMJ has an outstanding ability to withstand multidirectional forces.…”

“…It promoted BMSCs proliferation, migration, and chondrogenic differentiation, and inhibited chondrocytes apoptosis and hypertrophy to delay the progression of osteoarthritis. Meanwhile, PRP-derived exosomes inhibited the TNF-α release from chondrocytes and presented a potential in alleviating OA via WNT/β-catenin pathway (Zhang Y. et al, 2022). Alexander found that citrate-anticoagulated platelet-rich plasma-derived exosomes displayed a higher expression of SOX9 protein and a better inhibition effect on proinflammatory cytokine release compared to hyperacute serum-derived exosomes (Liu et al, 2019).…”

The Role of AIM2 Inflammasome in Knee Osteoarthritis

“…58,59 However, most studies have focused on the RNA and protein content of EVs, while little has been reported on the DNA carried within them. [60][61][62][63] Takahashi et al showed that EVs maintain cellular homeostasis and prevent aberrant activation of the innate immune response by expelling damaged DNA from cells, and when this process is impaired, the DNA they carry can activate inflammatory factors including the cGAS-STING pathway and the AIM2 inflammasome. 64 In the study of the gastrointestinal response to the chemotherapeutic agent irinotecan, Lian et al found that chemotherapy-induced the release of large amounts of double-stranded DNA from exosomes in the gastrointestinal tract, and this "auto-DNA" entered the cytoplasm of innate immune cells and activated AIM2 inflammasome.…”

Exosomes as Biochemistry Tools for Stem Cell Differentiation: A Novel Cell-Based Treatment for Diseases

“…These membranous exosomes contain proteins, mRNA, DNA, miRNA, lipids, and other molecules from the cytoplasm of their parent cell (Figure 1). In addition, multivesicular bodies can be sent to lysosomes from degradation or fuse with the plasma membrane and release exosomes via exocytosis (14). A variety of cell types secrete exosomes.…”