Biomechanical signals mediate cellular mechano-transduction and gene regulation.

摘要

Cartilage is a mechanosensitive tissue, which can perceive and respond to biomechnical signals. Despite the known importance of biomechanical signals in the etiopathogenesis of arthritic diseases, and their effectiveness in joint restoration, little is understood about their actions at the cellular level. Recent molecular approaches have revealed that specific biomechanical stimuli and cell interactions generate intracellular signals that are powerful inducers or suppressors of proinflammatory and reparative genes in chondrocytes. Biomechanical signals are perceived by cartilage in a magnitude, frequency, and time dependent manner. Static as well as dynamic biomechanical forces of high magnitudes induce proinflammatory genes and inhibit matrix synthesis. Contrarily, dynamic biomechanical signals of low/physiological magnitudes are potent anti-inflammatory signals that inhibit IL-1beta-induced proinflammatory gene transcription, as well as abrogate IL-1 b&d5; /TNF-alpha-induced inhibition of matrix synthesis. Recent studies have identified NF-kappaB transcription factors as key regulators of biomechanical signals-mediated proinflammatory as well as anti-inflammatory actions. These signals intercept multiple steps in the NF-kappaB signaling cascade to regulate cytokine gene expression. Taken together these findings provide insight into how biomechanical signals regulate inflammatory and reparative gene transcription, underscoring their potential in enhancing the ability of chondrocytes to curb inflammation in diseased joints.