Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway

Abstract

We first applied moderate fluid shear stress to nucleus pulposus cells. The correlation of AP-1 with type II collagen, proteoglycan, Cytokeratin 8 protein, MAP-1, MAP-2, and MAP-4 and the correlation of AP-1 with IL-1β, TNF-α, IL-6, IL-8, MIP-1, MCP-1, and NO were detected. Our results document that moderate fluid shear stress could activate the FAK-MEK5-ERK5-cFos-AP1 signaling pathway. AP1 could downregulate the construct factors of cytoskeleton such as type II collagen, proteoglycan, Cytokeratin 8 protein, MAP-1, MAP-2, and MAP-4 in nucleus pulposus cell after the fluid shear stress was loaded. AP1 could upregulate the inflammatory factors such as IL-1β, TNF-α, IL-6, IL-8, MIP-1, MCP-1, and NO in nucleus pulposus cell after the fluid shear stress was loaded. Taken together, our data suggested that moderate fluid shear stress may play an important role in the cytoskeleton of nucleus pulposus and surrounding inflammatory mediators by activating the FAK-MEK5-ERK5-cFos-AP1 signaling pathway, thereby affecting cell degeneration.