Figure 5

Effect of chemical inhibitors of CD44-ICD production on the reduced expression of SOX9 protein by cyclic tensile strain (CTS) loading. (A) GI254023X (GI), a chemical inhibitor of ADAM10, dose-dependently decreased both CD44-EXT and CD44-ICD bands upon CTS loading (0.5 Hz and 20% elongation for 12 hours). Densitometry of CD44-ICD/β-actin. Values are mean ± standard deviation from three independent experiments and expressed as n-fold increase compared to untreated control. (B) DAPT, a chemical inhibitor of γ-secretase, dose-dependently decreased production of the CD44-ICD band by CTS loading. At the same time, CD44-EXT accumulated in a dose-dependent manner. Densitometry of CD44-ICD/β-actin. Values are mean ± standard deviation of three independent experiments. (C,D) Both GI and DAPT effectively rescued the decrease in SOX9 expression by CTS loading (0.5 Hz and 20% elongation for 12 hours) in a dose-dependent manner.