Amarogentin Alleviates Osteoarthritis by Regulating Chondrocyte Proliferation and Autophagy

Abstract

Although amarogentin has been shown to play an amelioration role in several disease states, its role in osteoarthritis progression remains unexplored. To this end, we have examined the role of amarogentin in interleukin-1β-treated chondrocytes, a cell model of osteoarthritis. We observed that chondrocyte proliferation was attenuated after interleukin-1β treatment, which was reversed by amarogentin treatment. In addition, the protein expressions for matrix metalloproteinase-3 and matrix metalloproteinase-9 were enhanced, and collagen II was reduced after interleukin-1β treatment, but these changes were reversed by amarogentin treatment, indicating that amarogentin inhibited interleukin-1β-stimulated extracellular matrix degradation. Moreover, amarogentin strengthened interleukin-1β-triggered chondrocyte autophagy by enhancing LC3II/LC3I, Beclin1, and Atg7 levels and reducing the level of P62, a cargo adaptor protein that interacts with autophagic substrates and delivers them to autophagosomes for degradation. Besides, the expressions of p-AMPK/AMPK and SIRT1 proteins were diminished after interleukin-1β treatment, but these effects were restored by amarogentin treatment, illustrating that amarogentin activated the AMPK/SIRT1 pathway. In conclusion, amarogentin alleviates osteoarthritis by regulating chondrocyte proliferation and autophagy through the AMPK/SIRT1 pathway.