Potential of Exosomes for Diagnosis and Treatment of Joint Disease: Towards a Point-of-Care Therapy for Osteoarthritis of the Knee

Abstract

In the knee joint, articular cartilage injury can often lead to osteoarthritis of the knee (OAK). Currently, no point-of-care treatment can completely address OAK symptoms and regenerate articular cartilage to restore original functions. While various cell-based therapies are being developed to address OAK, exosomes containing various components derived from their cells of origin have attracted attention as a cell-free alternative. The potential for exosomes as a novel point-of-care treatment for OAK has been studied extensively, especially in the context of intra-articular treatments. Specific exosomal microRNAs have been identified as possibly effective in treating cartilage defects. Additionally, exosomes have been studied as biomarkers through their differences in body fluid composition between joint disease patients and healthy subjects. Exosomes themselves can be utilized as a drug delivery system through their manipulation and encapsulation of specific contents to be delivered to specific cells. Through the combination of exosomes with tissue engineering, novel sustained release drug delivery systems are being developed. On the other hand, many of the functions and activities of exosomes are unknown and challenges remain for clinical applications. In this review, the possibilities of intra-articular treatments utilizing exosomes and the challenges in using exosomes in therapy are discussed.

The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective

“…Due to the protective environment provided by EVs, many studies have highlighted the diagnostic advantages of EVs-miRNAs compared to the free-circulating miRNAs. 127 , 128 Furthermore, the expression level of EVs-miRNAs can be easily tested by collecting intra-articular synovial fluid and intuitively reflecting the joint condition due to its physical association with periarticular tissues like synovial membrane and articular cartilage. For example, Kolhe et al found altered profiles of exosomal miRNAs in synovial fluid of OA patients and demonstrated this alteration could be gender specific.…”

The Role of Extracellular Vesicles in Systemic Lupus Erythematosus

“…EVs can carry β -Amyloid, prion, and α -synuclein, thus spread disease-causing proteins in the brain, which may be involved in Alzheimer’s disease progression ( Nath et al, 2012 ; Arellano-Anaya et al, 2015 ; Lööv et al, 2016 ). Evidence shows that EV-associated miRNAs and lncRNAs play essential roles in the pathogenesis of osteoarthritis (OA), including OA diagnosis, pathogenesis, and treatment ( Maehara et al, 2021 ; Miao et al, 2021 ). In addition, EVs are involved in many physiological processes, such as intracellular communication, signal transduction, transport of genetic materials, and modulation of immune response ( Natasha et al, 2014 ).…”

The Research Progress of Exosomes in Osteoarthritis, With Particular Emphasis on the Therapeutic Effect

“…Late endosomes or multivesicular bodies (MVBs) are then formed through a series of changes. When MVBs fuse with the cell membrane, internal ILVs are released extracellularly as exosomes, which may then be absorbed by target cells ( Maehara et al, 2021 ) ( Figure 1 ).…”

“…Exosomes have a lipid bilayer membrane consisting of lipid raft constituents (such as cholesterol, sphingomyelin, and ceramide), tetraspanins (such as CD9, 63, and 81), and proteins (such as integrin, cell specific receptors, major histocompatibility complex class I and class II, and flotillin-1) ( Maehara et al, 2021 ). Proteins, lipids, and nucleic acids are carried by exosomes, including messenger RNA (mRNA), microRNA (miRNA), and long-chain non-coding RNA (lncRNA).…”