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

阿魏酸通过 SIRT1/AMPK/PGC-1α 信号通路抑制白细胞介素-1β 诱导的骨关节炎患者分离软骨细胞退化

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作者:Kewei Du, Xuchen Fang, Ziqiang Li

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.

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.

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.

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