Osteocytes are the most abundant and long-lived cells in bone, serving as primary regulators of bone remodeling. Besides playing critical roles in endocrine regulation and calcium-phosphate metabolism, osteocytes are primary responders to mechanical stimuli, perceiving and responding to these stimuli directly and indirectly. The process of mechanotransduction in osteocytes is a complex and finely tuned regulation involving interactions between the cell and its surrounding environment, neighboring cells, and various mechanosensors within the cells with distinct functions. The known major mechanosensors in osteocytes include primary cilia, piezo ion channels, integrins, extracellular matrix, and connexin-based intercellular junctions. These mechanosensors play crucial roles in osteocytes, perceiving and transducing mechanical signals to regulate bone homeostasis. This review aims to provide a systematic introduction to these five mechanosensors, offering new perspectives and insights into understanding how osteocytes respond to mechanical stimuli and maintain bone tissue homeostasis.
