An overview of mechanical microenvironment and mechanotransduction in intervertebral disc degeneration

Cellular mechanotransduction, essential for many biological functions, involves the conversion of mechanical signals into biochemical signals related to cell activities and metabolism. Physical factors in the local cellular microenvironment include external mechanical forces, mechanical stimulation generated by the extracellular matrix and intercellular mechanical interactions mediated through cell-cell adhesions. Intervertebral disc degeneration (IDD) is a complex pathological process involving diverse etiological contributors, such as mechanical wear, oxidative damage and nutritional deficiency. Notably, aberrant mechanical loading has been identified as a pivotal driver in both the initiation and progression of IDD. The mechanical microenvironment in intervertebral discs mainly includes pressure, tension, hydrostatic pressure, osmotic pressure and extracellular matrix stiffness. A thorough understanding of the mechanotransduction process of intervertebral disc cells in response to various mechanical stimuli and its regulatory mechanism is of great significance for the prevention and treatment of IDD. Here, therefore, we systematically review the research progress in understanding the mechanical microenvironment and mechanotransduction in IDD.