TNF-αInduced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2.
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-αand 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.
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Zhenhua
Z
Liu
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Liangbin
L
Gao
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Peng
P
Wang
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Zhongyu
Z
Xie
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Shuizhong
S
Cen
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Yuxi
Y
Li
Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Xiaohua
X
Wu
Institute of Orthopaedics and Traumatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Le
L
Wang
Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Hongjun
H
Su
Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Wen
W
Deng
Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Shan
S
Wang
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Deng
D
Li
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Jinteng
J
Li
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Yi
Y
Ouyang
Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Yanfeng
0000-0001-6409-821X
Y
Wu
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, China.
Huiyong
0000-0003-0638-0182
H
Shen