TNF-α Induced 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...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2017/4521324 |
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| author | Zhenhua Liu Liangbin Gao Peng Wang Zhongyu Xie Shuizhong Cen Yuxi Li Xiaohua Wu Le Wang Hongjun Su Wen Deng Shan Wang Deng Li Jinteng Li Yi Ouyang Yanfeng Wu Huiyong Shen |
| author_facet | Zhenhua Liu Liangbin Gao Peng Wang Zhongyu Xie Shuizhong Cen Yuxi Li Xiaohua Wu Le Wang Hongjun Su Wen Deng Shan Wang Deng Li Jinteng Li Yi Ouyang Yanfeng Wu Huiyong Shen |
| author_sort | Zhenhua Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cc1eebfc24f84c9ab054face3767f442 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-cc1eebfc24f84c9ab054face3767f4422025-02-03T01:27:34ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/45213244521324TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2Zhenhua Liu0Liangbin Gao1Peng Wang2Zhongyu Xie3Shuizhong Cen4Yuxi Li5Xiaohua Wu6Le Wang7Hongjun Su8Wen Deng9Shan Wang10Deng Li11Jinteng Li12Yi Ouyang13Yanfeng Wu14Huiyong Shen15Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaCenter for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaInstitute of Orthopaedics and Traumatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, ChinaCenter for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaCenter for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaCenter for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaCenter for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang Road West, Guangzhou 510120, ChinaAnkylosing 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.http://dx.doi.org/10.1155/2017/4521324 |
| spellingShingle | Zhenhua Liu Liangbin Gao Peng Wang Zhongyu Xie Shuizhong Cen Yuxi Li Xiaohua Wu Le Wang Hongjun Su Wen Deng Shan Wang Deng Li Jinteng Li Yi Ouyang Yanfeng Wu Huiyong Shen TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2 Stem Cells International |
| title | TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2 |
| title_full | TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2 |
| title_fullStr | TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2 |
| title_full_unstemmed | TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2 |
| title_short | TNF-α Induced the Enhanced Apoptosis of Mesenchymal Stem Cells in Ankylosing Spondylitis by Overexpressing TRAIL-R2 |
| title_sort | tnf α induced the enhanced apoptosis of mesenchymal stem cells in ankylosing spondylitis by overexpressing trail r2 |
| url | http://dx.doi.org/10.1155/2017/4521324 |
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