Ferulic acid suppresses interleukin-1β-induced degeneration of chondrocytes isolated from patients with osteoarthritis through the SIRT1/AMPK/PGC-1α signaling pathway

Abstract

Background: Interleukin-1β (IL-1β) is involved in osteoarthritis pathogenesis and mediates a series of toxic processes including the production of matrix metalloproteinase and inflammatory regulators which are suppressed by activation of silent information regulator 1 (SIRT1). We aimed to determine the effects of ferulic acid (FA) on IL-1β-induced osteoarthritis chondrocyte degeneration. Methods: We examined the effects of FA on osteoarthritis chondrocyte viability and SIRT1 activation. The impact of FA on IL-1β-induced osteoarthritis chondrocyte toxicity was determined by prostaglandin E2 (PGE2), nitrite, IL-6, components of the extracellular matrix, and markers of oxidative stress. Finally, we determined whether these effects were mediated through SIRT1 by inhibiting SIRT1 activity using SIRT1 inhibitor Sirtinol. Results: We found that FA activated SIRT1/AMPK/PGC-1α signaling pathway and attenuated IL-1β-induced osteoarthritis chondrocyte degeneration by suppressing the production of IL-6, PGE2, nitrite, Collagen I, Runx-2, MMP-1, MMP-3, and MMP-13, enhancing Collagen II and Aggrecan expression and inhibiting oxidative stress. Inhibition of SIRT1 by Sirtinol attenuated the protective effects of FA. Conclusion: Our findings reveal that FA prevents IL-1β-induced osteoarthritis chondrocyte toxicity, which suggests that FA may be a potential therapy for osteoarthritis and warrants further investigation for its clinical application.