Isorhamnetin inhibits mechanical stress-induced chondrocyte apoptosis through activation of the ROS/SRC/FOXO1...

Intervertebral disc degeneration (IDD), a chronic degenerative disease, is characterized by pain without a satisfactory therapeutic strategy. Excessive mechanical pressure contributes to the pathological development of IDD by inducing chondrocyte apoptosis in the cartilage endplate. Isorhamnetin (ISO) has been shown to have chondroprotective effects by promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis. In this study, we found that mechanical loading could inactivate the SRC/FOXO1 signaling pathway and increase chondrocyte apoptosis, leading to disc degeneration in rats. ISO neutralized mechanical loading-induced chondrocyte apoptosis and attenuated the progression of disc degeneration. However, activation of ROS/SRC/FOXO1 signaling by EPQpYEEIPIYL (EPQ) and H2O2 attenuated the biological effects of ISO on mechanical loading-treated chondrocytes. Therefore, ISO may protect against mechanical loading-induced injury and inhibit chondrocyte apoptosis through the activation of the ROS/SRC/FOXO1 signaling pathway.