Effect of autophagy induced by dexamethasone on senescence in chondrocytes

Mol Med Rep. 2016 Oct;14(4):3037-44. doi: 10.3892/mmr.2016.5662. Epub 2016 Aug 22.


The aim of the current study was to explore the effects of dexamethasone (DXM) on autophagy and senescence in chondrocytes. Collagen II and aggrecan were examined in normal chondrocytes isolated from Sprague‑Dawley rats. Following stimulation with DXM, LysoTracker Red staining, monodansylcadaverine (MDC) staining, green fluorescent protein‑red fluorescent protein‑light chain 3 (LC3) and western blotting were used to detect autophagy levels in the chondrocytes. Mechanistic target of rapamycin (mTOR) pathway‑associated molecules were investigated by western blotting. Cell senescence was analyzed by senescence‑associated (SA)‑β‑galactosidase (β‑gal) staining. A dose‑dependent increase in the number of autophagic vacuoles was observed in the DXM‑treated chondrocytes, as demonstrated by LysoTracker Red and MDC staining. A dose‑dependent increase in autophagosome formation was observed in the DXM‑treated chondrocytes. Expression of LC3‑II and beclin‑1 was increased by DXM, in particular in the cells treated with DXM for 4 days. However, P62 expression was reduced as a result of treatment. SA‑β‑gal staining indicated that DXM increased cell senescence. Notably, DXM‑induced cell senescence was exacerbated by the autophagic inhibitor 3‑MA. Autophagy induced by DXM protected chondrocytes from senescence, and it is suggested that the mTOR pathway may be involved in the activation of DXM‑induced autophagy.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Autophagy / drug effects*
  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Dexamethasone / pharmacology*
  • Male
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism


  • Anti-Inflammatory Agents
  • Dexamethasone
  • TOR Serine-Threonine Kinases