Eupatilin protects chondrocytes from apoptosis via activating sestrin2-dependent autophagy

Int Immunopharmacol. 2019 Oct:75:105748. doi: 10.1016/j.intimp.2019.105748. Epub 2019 Jul 12.

Abstract

Cartilage degradation is the main characterization of osteoarthritis (OA). Accumulating evidence suggests that chondrocyte apoptosis and autophagy are associated with cartilage degradation. Thus, we investigated the protective effect and underlying mechanism of eupatilin for treating OA. IL-1β was used to simulate OA in vitro. Data show that eupatilin treatment attenuated IL-1β-induced apoptosis of chondrocytes. Autophagy was also activated by eupatilin in a dose-dependent manner. Then, pretreatment with chloroquine (CQ), an autophagic inhibitor, decreased eupatilin-induced autophagy and increased apoptosis in the chondrocytes. To investigate the mechanism of eupatilin, the expressions of sestrin2 and mTOR were measured using Western blot; eupatilin upregulated sestrin2 but downregulated mTOR phosphorylation. The administration of sestrin2-siRNA significantly decreased autophagy and reversed the protective effect of eupatilin against chondrocyte apoptosis and degradation of the cartilage matrix. Thus, eupatilin can inhibit IL-1β-induced apoptosis via sestrin2-dependent autophagy in chondrocytes.

Keywords: Apoptosis; Autophagy; Eupatilin; Osteoarthritis; Sestrin2.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Flavonoids / pharmacology*
  • Interleukin-1beta
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Rats, Sprague-Dawley

Substances

  • Flavonoids
  • Interleukin-1beta
  • Nuclear Proteins
  • Sesn2 protein, rat
  • eupatilin