Epigenetic crosstalk in bone and cartilage disorders: Emerging role of extracellular vesicles

Extracellular vesicles (EVs) are complex phospholipidic structures that play a central role in intercellular communication. They encapsulate many signaling molecules, such as lipids, proteins, and nucleic acids, to modulate multiple biological events. Recent breakthroughs have revealed that EVs can reprogram epigenetic mechanisms through posttranslational modifications (PTMs) of histones or DNA methylation. Indeed, understanding the molecular mechanisms and consequences of epigenetic mechanisms plays a fundamental role in skeletal development and the pathogenesis of various bone and cartilage disorders. In this context, many studies have demonstrated that EVs can be a therapeutic tool to address joint diseases. The study of EVs that target epigenetic alterations and can be introduced as epidrugs is promising. This review seeks to compile and summarize recent findings on epigenetic modifications during bone and cartilage regeneration. Next, we outlined the potential of various sources of EVs and their roles in bone- and cartilage-related diseases. Finally, we discuss the use of miRNA-enriched EVs as epigenetic factors in the treatment of bone and cartilage diseases.