Perception and response of skeleton to mechanical stress.

• Sclerotin is the main structure to withstand mechanical stress, and osteocytes are the main sensitive cells to sense mechanical stress. • The extracellular matrix plays an important role in sensing, buffering, and transmitting mechanical stress. • F-actin is crucial for the activation of piezoelectric channels. • Osteocytes achieve osteogenesis or bone resorption by regulating other cells. Mechanical stress stands as a fundamental factor in the intricate processes governing the growth, development, morphological shaping, and maintenance of skeletal mass. The profound influence of stress in shaping the skeletal framework prompts the assertion that stress essentially births the skeleton. Despite this acknowledgment, the mechanisms by which the skeleton perceives and responds to mechanical stress remain enigmatic. In this comprehensive review, our scrutiny focuses on the structural composition and characteristics of sclerotin, leading us to posit that it serves as the primary structure within the skeleton responsible for bearing and perceiving mechanical stress. Furthermore, we propose that osteocytes within the sclerotin emerge as the principal mechanical-sensitive cells, finely attuned to perceive mechanical stress. And a detailed analysis was conducted on the possible transmission pathways of mechanical stress from the extracellular matrix to the nucleus. [ABSTRACT FROM AUTHOR]