Tension regulates the cartilage phenotypic expression of endplate chondrocytes through the α‐catenin/actin skeleton/Hippo pathway

TL;DR

This study shows how tension affects cartilage cells through a specific signaling pathway, which could help treat cartilage degeneration.

Contribution

The study identifies the α-Catenin/actin skeleton/Hippo pathway as a novel mechanism regulating tension signaling in endplate chondrocytes.

Findings

Tension activates the Hippo pathway and increases YAP phosphorylation in endplate chondrocytes.

YAP overexpression counteracts tension's inhibitory effect on extracellular matrix synthesis.

α-Catenin expression is upregulated by tension and mediates cytoskeletal and YAP changes.

Abstract

The study aimed to investigate the regulatory mechanism of intracellular tension signaling in endplate chondrocytes and its impact on extracellular matrix synthesis. Human endplate chondrocytes were subjected to tension load using Flexcell FX‐5000™, and changes in phenotype, morphology, and the expression of Hippo signaling pathway and α‐Catenin were assessed through various techniques. Through the overexpression of YAP and inhibition of α‐Catenin, the study clarified the intracellular tension signaling pathway and its regulation of extracellular matrix synthesis in endplate cartilage. In vitro‐cultured human endplate chondrocytes significantly suppressed phenotype‐related genes and proteins, accompanied by distinct changes in cytoskeleton morphology. Tension activation resulted in the substantial activation of the Hippo pathway, increased phosphorylation of YAP, and reduced nuclear translocation of YAP. YAP overexpression alleviated the inhibitory effect of tension on extracellular matrix synthesis in endplate chondrocytes. Tension also upregulated the expression of α‐Catenin in endplate chondrocytes, which was attenuated by inhibiting α‐Catenin expression, thereby reducing the impact of tension on cytoskeletal morphology and YAP nuclear translocation. Taken together, the α‐Catenin/actin skeleton/Hippo‐coupled network is a crucial signaling pathway for tension signaling in endplate chondrocytes, providing potential therapeutic targets for the treatment of endplate cartilage degeneration.

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