The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis

Abstract

Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates that non-coding RNAs can be shuttled among the cells and tissues via EVs, allowing non-coding RNAs to reach distant cells and exert systemic effects. Resident bone cells, including osteoclasts, osteoblasts, osteocytes, and endothelial cells, are tightly regulated by non-coding RNAs, and many of them can be exported from the cells to neighboring ones through EVs, triggering pathological conditions. For these reasons, researchers have also started to exploit EVs as a theranostic tool to address osteoporosis. In this review, we summarize some recent findings regarding the EVs’ involvement in the fine regulation of non-coding RNAs in the context of bone metabolism and osteoporosis.

Extracellular Vesicles-Mediated Transfer of miRNA Let-7b from PC3 Cells to Macrophages

“…Several studies reported that miRNAs could be transferred between cells via EVs [ 6 , 7 , 21 ]; thus, we wondered whether PC3-derived EVs could transfer miRNA Let-7b to THP-1 cells. We exposed THP-1 monocytic cells, after TPA differentiation into M0 macrophages, to 100 μg/mL PC3-EVs for different times and observed the appearance of red fluorescent EV-like particles in the cytoplasm after 30 min incubation ( Figure 3 .…”

Blood factors as biomarkers in osteoporosis: points from the COVID-19 era

“…Evidently, this would require a reorientation of healthcare systems to meet the challenge set forth by OP, ensuring adequate care, health promotion, and treatment equity and avoiding the fragmentation of the clinical route. Over time, different biomarkers have been proposed for OP, among which those most discussed are specific multifunctional proteins (e.g., Annexin A2 and prolyl 4-hydroxylase) and circulating miRNAs (e.g., miR-223-3p, miR-148a-3p, miR-125b-5p, and miR-124-3p) [ 16 , 54 , 55 ]. However, the information related to these biomarkers during OP are still limited due to the different types of samples (serum, circulating monocytes, bone marrow, and bone tissue) obtained from patients of different sexes and different ethnic groups with low BMD or bone fractures and compared with healthy or osteoarthritis patients [ 48 , 49 ].…”

“…Recent breakthroughs have highlighted different methods starting from noncoding RNAs [microRNAs (miRNAs) and long noncoding RNAs (lncRNAs)], proteins, enzymes, or hormones [ 15. , 16. , 17.…”

Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

“…The majority of EV research has focused on miRNA, but other RNA species that can be found in EVs include messenger RNA (mRNA), long non-coding RNA (lncRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), RNA repeats, and circular RNA (circRNA) [ 82 , 83 , 84 , 85 , 86 ]. EV cargo can also include DNA and other genetic materials that reflect their cellular origin [ 87 , 88 ].…”