Abstract
Exosomes are the small extracellular vesicles secreted by cells for intercellular communication. Exosomes are rich in therapeutic cargos such as microRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids. Recently, many studies have focused on miRNAs as a promising therapeutic factor to support cartilage regeneration. Exosomes are known to contain a substantial amount of a variety of miRNAs. miRNAs regulate the post-transcriptional gene expression by base-pairing with the target messenger RNA (mRNA), leading to gene silencing. Several exosomal miRNAs have been found to play a role in cartilage regeneration by promoting chondrocyte proliferation and matrix secretion, reducing scar tissue formation, and subsiding inflammation. The exosomal miRNA cargo can be modulated using techniques such as cell transfection and priming as well as post-secretion modifications to upregulate specific miRNAs to enhance the therapeutic effect. Exosomes are delivered to the joints through direct injection or via encapsulation within a scaffold for sustained release. To date, exosome therapy for cartilage injuries has yet to be optimized as the ideal cell source for exosomes, and the dose and method of delivery have yet to be identified. More importantly, a deeper understanding of the role of exosomal miRNAs in cartilage repair is paramount for the development of more effective exosome therapy.
Highlights
We summarize the roles of exosomal miRNAs in cartilage regeneration
The smallest form of extracellular vesicle (EV), with diameters ranging from 30–150 nm [78], are usually synthesized through an endosomal-sorting complex required for transport (ESCRT)dependent or ESCRT-independent pathways [79,80,81,82]
The mature miRNA attaches to an argonaute (AGO) protein to form the core of the RNA-induced silencing complex (RISC), which subsequently interacts with target messenger RNA (mRNA) to regulate gene expression
Summary
Regardless of the treatment approaches, current interventions aim to prevent further damage and achieve symptoms control. Regenerative medicine is a new approach introduced in the last two decades to promote the regeneration of damaged cartilage. This approach is unique as it can stimulate cartilage regeneration, which cannot be achieved with conventional treatments. Exosomes are rich in proteins, lipids, and nucleic acids and have been documented to promote cartilage regeneration [7,8]. A battery of miRNAs was found to be involved in cartilage regeneration [9,10,11]. We summarize the roles of exosomal miRNAs in cartilage regeneration. We discuss the techniques used to modify the miRNA cargos of exosomes
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