Exosomes in Extracellular Matrix Bone Biology

Abstract

Exosomes were believed to be nanosized vesicles derived from the multivesicular body. Reports now suggest that nanovesicles could bud directly from the plasma membrane. However, the exosome cargo is cell-type specific and is derived from the parent cell. In the bone matrix, several intracellular proteins lacking a signal peptide are transported to the ECM by exosomes. Besides proteins, several mRNA, miRNA, and lipids are exported to the ECM by bone cells and bone marrow stromal cells. Recent evidence suggests that several of the functional components in the cargo could regulate processes of bone formation, inhibit osteoclast activity, and promote fracture repair. Exosomes are powerful cellular molecular machines produced without human intervention and packaged with physiological cargo that could be utilized for molecular therapy in several skeletal disorders such as osteoporosis, osteogenesis imperfecta, and fracture healing. Although much work has been done, there is a lot of information that is still unknown, as exosomes contain a multitude of molecules whose identity and function have yet to be identified.

Circulating miR-34a and Bone Mineral Density of Brazilian Very-Old Adults

“…Besides all, the most remarkable limitation may be represented by the difficulty of relating findings in a peripheral blood sample with pathophysiological processes in specific tissues/organs. In this respect, one should note that bonederived exosomes are released into the extracellular environment [37], and it is plausible that at least part of the microRNA content in the whole blood may reflect concentrations (and imbalances) existing elsewhere, including the bone millieu.…”

Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases

“…Another possibility is the use of EVs from pre-conditioned MSCs or modified EVs overexpressing proteins, miRNAs and so forth, to potentiate their regenerative properties. Nevertheless, it should be taken into account that endogenous EVs can be released by BM-MSCs, osteoblasts, osteoclasts, osteocytes, endothelial cells and immune cells leading to a complex communication network which plays an important role in bone formation, repair and remodeling (reviewed in References [98,99]). Further studies are required to identify the active components and dissect the mechanisms involved in these processes as well as their modification by the therapeutic administration of MSC EVs.…”

Potential Therapeutic Applications of Exosomes in Bone Regenerative Medicine

“…For example, heat-shock protein 70 (HSP70), which can be used as a marker of BMSCs-Exo, is downregulated in human MSC-Exos and negatively affects osteogenic and chondrogenic differentiation. Similarly, down-regulation of heat shock protein B8 (HSPB8) can reduce the formation of dental pulp stem cells, and osteogenic differentiation ability [109][110][111]. Overall, the specific biological mechanisms of some functional proteins to promote fracture healing are not fully understood, and further detailed researches will be needed.…”