Effect of autophagy induced by dexamethasone on senescence in chondrocytes

Xue,Enxing; Zhang,Yu; Song,Bing; Xiao,Jun; Shi,Zhanjun

doi:10.3892/mmr.2016.5662

Effect of autophagy induced by dexamethasone on senescence in chondrocytes

Authors:
- Enxing Xue
- Yu Zhang
- Bing Song
- Jun Xiao
- Zhanjun Shi
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Affiliations: Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Orthopedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: August 22, 2016 https://doi.org/10.3892/mmr.2016.5662
Pages: 3037-3044
Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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