Vanillic acid protects vertebral endplate chondrocytes against oxidative stress and inflammation via Nrf-2/HO-1 pathway.

Cartilage endplate (CEP) plays essential roles in the initiation and progression of intervertebral disc degeneration. Vanillic acid (VA) is widely used as a food additive and has been shown to exert cardioprotective, anti-inflammatory, and antioxidant effects. Nevertheless, the specific effects and underlying mechanisms of VA on CEP chondrocytes have not been fully elucidated. The present study aimed to explore the impacts of VA on CEP degeneration and clarify its potential molecular mechanisms. To simulate the pathological microenvironment of IVDD, tumor necrosis factor-α (TNF-α) and tert-butyl hydroperoxide (TBHP) were used to treat CEP chondrocytes, and the regulatory effect of VA on these cells was examined. Additionally, an IVDD mouse model was constructed by transecting the bilateral facet joints to evaluate the in vivo protective role of VA. Our results showed that VA could protect against oxidative stress and pro-inflammatory cytokines induced cartilage endplate degeneration and calcification. In vivo experiments further confirmed that VA was capable of mitigating the development of IVDD and CEP calcification. The protective effects of VA were associated with activation of the Nrf-2/HO-1 signaling pathway, accompanied by mitophagy-associated changes and attenuation of ferroptosis-associated alterations. These effects may contribute to the alleviation of redox imbalance and mitochondrial dysfunction, thereby improving chondrocyte survival. Collectively, our findings suggest that VA may represent a promising therapeutic candidate for the prevention and treatment of IVDD.