Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression
Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro culture results in loss of MSC stemness. The inflammation that occurs at stem cell transplant sites (such as that resulting from TNF-α) is a contributing factor for stem...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/6568394 |
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| author | Xudong Wang Tongzhou Liang Jincheng Qiu Xianjian Qiu Bo Gao Wenjie Gao Chengjie Lian Taiqiu Chen Yuanxin Zhu Anjing Liang Peiqiang Su Yan Peng Dongsheng Huang |
| author_facet | Xudong Wang Tongzhou Liang Jincheng Qiu Xianjian Qiu Bo Gao Wenjie Gao Chengjie Lian Taiqiu Chen Yuanxin Zhu Anjing Liang Peiqiang Su Yan Peng Dongsheng Huang |
| author_sort | Xudong Wang |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro culture results in loss of MSC stemness. The inflammation that occurs at stem cell transplant sites (such as that resulting from TNF-α) is a contributing factor for stem cell treatment failure. Currently, there is little evidence regarding the protective role of melatonin with regard to the negative effects of TNF-α on the stemness of MSCs. In this study, we report a melatonin-based method to reduce the inflammatory effects on the stemness of bone marrow mesenchymal stem cells (BMMSCs). The results of colony formation assays, Alizarin red staining, western blotting, and reverse transcription-polymerase chain reactions suggest that melatonin can reverse the inflammatory damage caused by TNF-α treatment in the third, seventh, and tenth generations of primary BMMSCs (vs. control and the TNF-α-treated group). Meanwhile, a detailed analysis of the molecular mechanisms showed that the melatonin receptor and YAP signaling pathway are closely related to the role that melatonin plays in negative inflammatory effects against BMMSCs. In addition, in vivo experiments showed that melatonin could reverse the damage caused by TNF-α on bone regeneration by BMMSCs in nude mice. Overall, our results suggest that melatonin can reverse the loss of stemness caused by inflammatory factor TNF-α in BMMSCs. Our results also provide a practical strategy for the application of BMMSCs in tissue engineering and cell therapy. |
| format | Article |
| id | doaj-art-dc919528f6204ede876090537611b22f |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-dc919528f6204ede876090537611b22f2025-02-03T06:11:32ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/65683946568394Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP ExpressionXudong Wang0Tongzhou Liang1Jincheng Qiu2Xianjian Qiu3Bo Gao4Wenjie Gao5Chengjie Lian6Taiqiu Chen7Yuanxin Zhu8Anjing Liang9Peiqiang Su10Yan Peng11Dongsheng Huang12Department of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, ChinaMesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro culture results in loss of MSC stemness. The inflammation that occurs at stem cell transplant sites (such as that resulting from TNF-α) is a contributing factor for stem cell treatment failure. Currently, there is little evidence regarding the protective role of melatonin with regard to the negative effects of TNF-α on the stemness of MSCs. In this study, we report a melatonin-based method to reduce the inflammatory effects on the stemness of bone marrow mesenchymal stem cells (BMMSCs). The results of colony formation assays, Alizarin red staining, western blotting, and reverse transcription-polymerase chain reactions suggest that melatonin can reverse the inflammatory damage caused by TNF-α treatment in the third, seventh, and tenth generations of primary BMMSCs (vs. control and the TNF-α-treated group). Meanwhile, a detailed analysis of the molecular mechanisms showed that the melatonin receptor and YAP signaling pathway are closely related to the role that melatonin plays in negative inflammatory effects against BMMSCs. In addition, in vivo experiments showed that melatonin could reverse the damage caused by TNF-α on bone regeneration by BMMSCs in nude mice. Overall, our results suggest that melatonin can reverse the loss of stemness caused by inflammatory factor TNF-α in BMMSCs. Our results also provide a practical strategy for the application of BMMSCs in tissue engineering and cell therapy.http://dx.doi.org/10.1155/2019/6568394 |
| spellingShingle | Xudong Wang Tongzhou Liang Jincheng Qiu Xianjian Qiu Bo Gao Wenjie Gao Chengjie Lian Taiqiu Chen Yuanxin Zhu Anjing Liang Peiqiang Su Yan Peng Dongsheng Huang Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression Stem Cells International |
| title | Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression |
| title_full | Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression |
| title_fullStr | Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression |
| title_full_unstemmed | Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression |
| title_short | Melatonin Reverses the Loss of Stemness Induced by TNF-α in Human Bone Marrow Mesenchymal Stem Cells through Upregulation of YAP Expression |
| title_sort | melatonin reverses the loss of stemness induced by tnf α in human bone marrow mesenchymal stem cells through upregulation of yap expression |
| url | http://dx.doi.org/10.1155/2019/6568394 |
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