Emerging Role of Extracellular Vesicles in Bone Remodeling.

Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes, microvesicles, and apoptotic bodies. EVs are released by most cell types, such as bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone-remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor β1) to osteoblasts and regulate bone formation. In addition, EVs can deliver cytokines, such as RANK (receptor activator of nuclear factor κB) and RANKL (RANK ligand), and microRNAs, such as miR-218 and miR-148a, to modulate osteoclast differentiation during bone resorption. EVs also transfer bioactive molecules and have targeted therapies in bone-related diseases. Moreover, bioactive molecules in EVs are biomarkers in bone-related diseases. We highlight the emerging role of EVs in bone remodeling during physiologic and pathologic conditions and summarize the role of EVs in tooth development and regeneration. At the end of this review, we discuss the challenges of EV application in the treatment of bone diseases.