General aspects of extracellular vesicles in bone formation and remodeling

Skeletal homeostasis is maintained by the concerted functions of bone cells. Hierarchical activities of bone-forming osteoblasts, mechanosensing osteocytes, and bone-resorbing osteoclasts ensure skeletal development, growth, and renewal. Skeletal functions must be kept balanced throughout life, and, in this context, various means of cell–cell communication play key roles for the physiological alternation of bone formation and resorption. Extracellular vesicles are important mediators of cell–cell communication, and, in bone, they contribute to matrix mineralization. Osteoblasts, osteocytes, and osteoclasts not only communicate among them but also with the surrounding microenvironment through extracellular vesicles, resulting in a plethora of coordinated activities also involving hematopoietic cells, vascular cells, stromal cells, and bone marrow adipocytes. This chapter will offer a global view of the known skeletal pathophysiological functions influenced by the extracellular vesicles. Calcifying matrix vesicles, as they are described in detail elsewhere in this book, will not be covered in this chapter.