Telmisartan Mitigates TNF-α-Induced Type II Collagen Reduction by Upregulating SOX-9

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)-induced degradation of extracellular matrix (ECM), such as type II collagen in chondrocytes, plays an important role in the development of osteoarthritis (OA). Telmisartan, an angiotensin II (Ang-II) receptor blocker, is a licensed drug used for the treatment of hypertension. However, the effects of Telmisartan in tumor necrosis factor-alpha (TNF-alpha)-induced damage to chondrocytes and the progression of OA are unknown. In this study, we found that treatment with Telmisartan attenuated TNF-a-induced oxidative stress by reducing the levels of mitochondrial reactive oxygen species (ROS) and the production of protein carbonyl in human C28/I2 chondrocytes. Interestingly, Telmisartan inhibited TNF-alpha-induced expression and secretions of proinflammatory mediators such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and monocyte chemotactic protein 1 (MCP-1). Notably, stimulation with TNF-a reduced the levels of type II collagen at both the mRNA and the protein levels, which was rescued by the treatment with Telmisartan. Mechanistically, we found that Telmisartan restored TNF-alpha-induced reduction of SOX-9. Silencing of SOX-9 blocked the inhibitory effects of Telmisartan against TNF-ainduced degradation of type II collagen. These findings suggest that Telmisartan might be a potential and promising agent for the treatment of OA.

Automated summary

The study showed that Telmisartan attenuated oxidative stress induced by TNF-α and inhibited the expression and secretion of proinflammatory mediators. It also rescued the reduction of type II collagen levels caused by TNF-α, making it a potential agent for the treatment of OA.