TGF-β/SMAD signaling inhibits intermittent cyclic mechanical tension-induced degeneration of endplate chondrocytes by regulating the miR-455-5p/RUNX2 axis.

A mechanical stimulation plays a pivotal role in maintaining normal cartilage function. Our objective was to reveal the mechanism of action of the tension-sensitive molecule miR-455-5p in the degeneration of endplate chondrocytes and to identify whether the transforming growth factor beta (TGF-β)/SMAD signaling pathway has a regulatory effect on it. The expression profiles of members of the TGF-β/SMAD pathway, miR-455-5p, and RUNX2 were determined by microRNA microarray analysis, reverse transcription quantitative polymerase chain reaction, luciferase reporter assay, and Western blot analysis. Intermittent cyclic mechanical tension (ICMT) induced the degeneration of endplate chondrocytes without affecting their viability. The tension-sensitive molecule miR-455-5p specifically bound to RUNX2, a gene involved in the degeneration of endplate chondrocytes. Activation of the TGF-β/SMAD signaling pathway upregulated miR-455-5p expression and thus inhibited RUNX2 levels. Therefore, the TGF-β/SMAD signaling pathway inhibits the ICMT-induced degeneration of endplate chondrocytes by regulating the miR-455-5p/RUNX2 axis.