Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment

Abstract

Osteoarthritis (OA) has remained a prevalent public health problem worldwide over the past decades. OA is a global challenge because its specific pathogenesis is unclear, and no effective disease-modifying drugs are currently available. Exosomes are small and single-membrane vesicles secreted via the formation of endocytic vesicles and multivesicular bodies (MVBs), which are eventually released when MVBs fuse with the plasma membrane. Exosomes contain various integral surface proteins derived from cells, intercellular proteins, DNAs, RNAs, amino acids, and metabolites. By transferring complex constituents and promoting macrophages to generate chemokines and proinflammatory cytokines, exosomes function in pathophysiological processes in OA, including local inflammation, cartilage calcification and degradation of osteoarthritic joints. Exosomes are also detected in synovial fluid and plasma, and their levels continuously change with OA progression. Thus, exosomes, specifically exosomal miRNAs and lncRNAs, potentially represent multicomponent diagnostic biomarkers for OA. Exosomes derived from various types of mesenchymal stem cells and other cell or tissue types affect angiogenesis, inflammation, and bone remodeling. These exosomes exhibit promising capabilities to restore OA cartilage, attenuate inflammation, and balance cartilage matrix formation and degradation, thus demonstrating therapeutic potential in OA. In combination with biocompatible and highly adhesive materials, such as hydrogels and cryogels, exosomes may facilitate cartilage tissue engineering therapies for OA. Based on numerous recent studies, we summarized the latent mechanisms and clinical value of exosomes in OA in this review.

Extracellular Vesicles and Hydrogels: An Innovative Approach to Tissue Regeneration

“…Exosomal miRNAs (such as miR-100–5p, miR-135b, miR-92a-3p, miR-140–5, miR-23b, miR-125b, miR-126–3p, miR-320) and lncRNAs like KLF3-AS1 and their interactions with diverse signaling pathways are primarily responsible for the therapeutic potential of MSCs-sEVs in the treatment of articular cartilage and OA. , The function of miRNAs in sEVs derived from synovial fluid, focusing on their impact on chondrocyte inflammation, proliferation, and survival, as well as their potential effect on cartilage degeneration in an OA model in rats was examined. Nineteen miRNAs were identified whose expression levels differed between OA patients and healthy controls.…”

Advances in the Study of Exosomes as Drug Delivery Systems for Bone-Related Diseases

“…Exosomes, as key vehicles for intercellular signal transmission, provide a more advantageous way to evaluate the pathological cells or tissue morphology in osteoarthritis [ 107 ]. In addition to promoting angiogenesis, bone remodeling, and chondrocyte proliferation and migration, exosomes can inhibit osteoarthritic chondrocyte apoptosis and reduce cartilage inflammation [ 107 ].…”

“…Exosomes, as key vehicles for intercellular signal transmission, provide a more advantageous way to evaluate the pathological cells or tissue morphology in osteoarthritis [ 107 ]. In addition to promoting angiogenesis, bone remodeling, and chondrocyte proliferation and migration, exosomes can inhibit osteoarthritic chondrocyte apoptosis and reduce cartilage inflammation [ 107 ]. Therefore, exosomes derived from BMSCs, adipose mesenchymal stem cells (AMSCs), synovial mesenchymal stem cells (SMSCs), human embryonic stem cells (HESCs), and other types of MSCs can be used as DDS to treat osteoarthritis [ 108 ] ( Figure 5 ).…”

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.…”