Osteocyte-Derived Extracellular Vesicles: Bridging the Gap in Skeletal Physiology and Pathophysiology.

PURPOSE OF REVIEW: Osteocytes are the most abundant cells in bone and serve as central skeletal regulators. Recent findings from our and other groups demonstrate that beyond soluble mediators, osteocytes communicate by releasing extracellular vesicles (EVs). This review provides a systematic overview of osteocyte-derived EVs and highlights their importance in diagnostic and therapeutic innovation.

RECENT FINDINGS: Accumulating evidence has linked osteocyte mechanotransduction to EV biogenesis and secretion. Mechanically induced calcium oscillations and signaling pathways impact load-induced EV release. Under normal conditions, osteocyte-derived EVs contribute to local and systemic intercellular communication within experimental models, whereas their direct role in immune-microenvironment remodeling remains insufficiently defined. In pathological states, alterations in osteocyte EV release and cargo composition are associated with both benign diseases and malignancies. Engineered osteocyte-derived EVs and EV-inspired delivery systems are being investigated as cell-free therapeutic platforms for skeletal regeneration. Continued research in osteocyte-derived EVs will deepen understanding of bone communication networks and resolve the principal conceptual and technical challenges.