Pantothenic acid alleviates osteoarthritis progression by inhibiting inflammatory response and ferroptosis through the SIRT1/Nrf2 signaling pathway.

Osteoarthritis (OA) is a degenerative joint disease that is a major cause of deformity, swelling, pain and even loss of function in the knee joints of the elderly. Pantothenic acid (PA) plays a protective role in many organs due to its antioxidant and anti-inflammatory properties. Herein, we aimed to assess the protective role of PA on osteoarthritis and investigate the underlying molecular mechanism. The levels of inflammatory factors (IL-1β and TNF-α) in knee tissues were measured by ELISA. The Safranin O-Fast Green staining was used to assess the severity of OA and the H&E staining was used to assess the degree of synovitis. In vitro, the levels of iron, MDA, GSH were measured by the detection kits. Western blotting was used to assess the levels of signaling-related proteins. Our results showed that PA significantly attenuated the degree of cartilage degeneration in the MIA-induced osteoarthritis model. PA also reduced the expression of IL-1β, TNF-α, MMP1 and MMP3. In vitro, PA effectively reduced the concentrations of MMP1 and MMP3 in IL-1β-stimulated chondrocytes. PA decreased the levels of Fe and MDA, while increasing GSH production and GPX4 and SLC7A11 expression in IL-1β-induced chondrocytes. Meanwhile, we found that PA was able to inhibit the phosphorylation level of p65, IκB protein in chondrocytes, which effectively blocked the NF-κB signaling pathway. Furthermore, PA also increased the level of SIRT1, Nrf2, and HO-1 protein expression. In addition, the inhibition of PA on IL-1β-induced MMPs production and ferroptosis were inhibited by the SIRT1 inhibitor EX-527. In conclusion, PA inhibited chondrocyte ferroptosis and cartilage destruction in osteoarthritis. The mechanism was through activating SIRT1/Nrf2 signaling pathway.