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Stem Cells International
Volume 2017, Article ID 4521324, 14 pages
https://doi.org/10.1155/2017/4521324
Research Article

TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2

1Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China
2Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China
3Institute of Orthopaedics and Traumatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China

Correspondence should be addressed to Yanfeng Wu; moc.621@ncgnefnayuw and Huiyong Shen; moc.nuyila@gnoyiuhnehs

Received 22 July 2016; Accepted 4 December 2016; Published 15 January 2017

Academic Editor: Silvia Brunelli

Copyright © 2017 Zhenhua Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Ankylosing spondylitis (AS) is an autoimmune disease with unknown etiology. Dysregulated mesenchymal stem cells (MSCs) apoptosis may contribute to the pathogenesis of autoimmune diseases. However, apoptosis of MSCs from patients with AS (ASMSCs) has not been investigated yet. The present study aims to assess the apoptosis of bone marrow-derived ASMSCs and to investigate the underlying mechanisms of altered ASMSCs apoptosis. We successfully induced the apoptosis of ASMSCs and MSCs from healthy donors (HDMSCs) using the combination of tumor necrosis factor alpha (TNF-α) and cycloheximide (CHX). We found that ASMSCs treated with TNF-α and CHX showed higher apoptosis levels compared to HDMSCs. During apoptosis, ASMSCs expressed significantly more TRAIL-R2, which activated both the death receptor pathway and mitochondria pathway by increasing the expression of FADD, cleaved caspase-8, cytosolic cytochrome C, and cleaved caspase-3. Inhibiting TRAIL-R2 expression using shRNA eliminated the apoptosis differences between HDMSCs and ASMSCs by partially reducing ASMSCs apoptosis but minimally affecting that of HDMSCs. Furthermore, the expression of FADD, cleaved caspase-8, cytosolic cytochrome C, and cleaved caspase-3 were comparable between HDMSCs and ASMSCs after TRAIL-R2 inhibition. These results indicated that increased TRAIL-R2 expression results in enhanced ASMSCs apoptosis and may contribute to AS pathogenesis.