P-Coumaric Acid Attenuates IL-1β-Induced Inflammatory Responses and Cellular Senescence in Rat Chondrocytes.

Abstract

Osteoarthritis (OA) is a common chronic inflammatory joint disease characterized by cartilage degradation. p-Coumaric acid (PCA), a dietary phenolic compound, has exerted anti-inflammatory and anti-oxidative activities in various diseases. However, the effects of PCA on OA have not been reported. In the present study, we aimed to investigate the effects of PCA on interleukin-1β(IL-1β)-induced inflammatory responses and cellular senescence in rat chondrocytes. Our results revealed that PCA remarkably downregulated IL-1β-induced inflammatory factors such as COX2 and iNOS and cartilage-degrading enzymes like matrix metalloproteinases (MMP1, MMP3, and MMP13) and aggrecanases (ADAMTS4 and ADAMTS5) in chondrocytes. The IL-1β-induced degradation of cartilage matrix (collagen II and aggrecan) could also be suppressed by PCA. Besides, PCA treatment effectively inhibited the IL-1β-induced p16INK4a protein expression and SAβ-gal activities in vitro. Mechanism analysis showed that PCA suppressed IL-1β-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. In vivo, we also found that PCA could alleviate the development of OA in a rat model. Altogether, our findings implicate that p-coumaric acid attenuates IL-1β-induced inflammatory responses and cellular senescence via inhibition of the MAPK and NF-κB signaling pathway in chondrocytes, and p-coumaric acid may be a promising candidate for the treatment of osteoarthritis.