Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha
Accumulation of reactive oxygen species (ROS), which can be induced by inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This process can contribute to the imbalance of bone rem...
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2019-01-01
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Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2019/6403967 |
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author | Xianjian Qiu Xudong Wang Jincheng Qiu Yuanxin Zhu Tongzhou Liang Bo Gao Zizhao Wu Chengjie Lian Yan Peng Anjing Liang Peiqiang Su Dongsheng Huang |
author_facet | Xianjian Qiu Xudong Wang Jincheng Qiu Yuanxin Zhu Tongzhou Liang Bo Gao Zizhao Wu Chengjie Lian Yan Peng Anjing Liang Peiqiang Su Dongsheng Huang |
author_sort | Xianjian Qiu |
collection | DOAJ |
description | Accumulation of reactive oxygen species (ROS), which can be induced by inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This process can contribute to the imbalance of bone remodeling, which ultimately leads to osteoporosis. Therefore, reducing the ROS generation during osteogenesis of BMSCs may be an effective way to reverse the impairment of osteogenesis. Melatonin (MLT) has been reported to act as an antioxidant during cell proliferation and differentiation, but its antioxidant effect and mechanism of action during osteogenesis of MSCs in the inflammatory microenvironment, especially in the presence of TNF-α, remain unknown and need further study. In our study, we demonstrate that melatonin can counteract the generation of ROS and the inhibitory osteogenesis of BMSCs induced by TNF-α, by upregulating the expression of antioxidases and downregulating the expression of oxidases. Meanwhile, MLT can inhibit the phosphorylation of p65 protein and block the degradation of IκBα protein, thus decreasing the activity of the NF-κB pathway. This study confirmed that melatonin can inhibit the generation of ROS during osteogenic differentiation of BMSCs and reverse the inhibition of osteogenic differentiation of BMSCs in vitro, suggesting that melatonin can antagonize TNF-α-induced ROS generation and promote the great effect of osteogenic differentiation of BMSCs. Accordingly, these findings provide more evidence that melatonin can be used as a candidate drug for the treatment of osteoporosis. |
format | Article |
id | doaj-art-c4206312b69f46cd9320a774faee9da9 |
institution | Kabale University |
issn | 1687-966X 1687-9678 |
language | English |
publishDate | 2019-01-01 |
publisher | Wiley |
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series | Stem Cells International |
spelling | doaj-art-c4206312b69f46cd9320a774faee9da92025-02-03T06:05:21ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/64039676403967Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-AlphaXianjian Qiu0Xudong Wang1Jincheng Qiu2Yuanxin Zhu3Tongzhou Liang4Bo Gao5Zizhao Wu6Chengjie Lian7Yan Peng8Anjing Liang9Peiqiang Su10Dongsheng Huang11Department of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaAccumulation of reactive oxygen species (ROS), which can be induced by inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This process can contribute to the imbalance of bone remodeling, which ultimately leads to osteoporosis. Therefore, reducing the ROS generation during osteogenesis of BMSCs may be an effective way to reverse the impairment of osteogenesis. Melatonin (MLT) has been reported to act as an antioxidant during cell proliferation and differentiation, but its antioxidant effect and mechanism of action during osteogenesis of MSCs in the inflammatory microenvironment, especially in the presence of TNF-α, remain unknown and need further study. In our study, we demonstrate that melatonin can counteract the generation of ROS and the inhibitory osteogenesis of BMSCs induced by TNF-α, by upregulating the expression of antioxidases and downregulating the expression of oxidases. Meanwhile, MLT can inhibit the phosphorylation of p65 protein and block the degradation of IκBα protein, thus decreasing the activity of the NF-κB pathway. This study confirmed that melatonin can inhibit the generation of ROS during osteogenic differentiation of BMSCs and reverse the inhibition of osteogenic differentiation of BMSCs in vitro, suggesting that melatonin can antagonize TNF-α-induced ROS generation and promote the great effect of osteogenic differentiation of BMSCs. Accordingly, these findings provide more evidence that melatonin can be used as a candidate drug for the treatment of osteoporosis.http://dx.doi.org/10.1155/2019/6403967 |
spellingShingle | Xianjian Qiu Xudong Wang Jincheng Qiu Yuanxin Zhu Tongzhou Liang Bo Gao Zizhao Wu Chengjie Lian Yan Peng Anjing Liang Peiqiang Su Dongsheng Huang Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha Stem Cells International |
title | Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha |
title_full | Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha |
title_fullStr | Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha |
title_full_unstemmed | Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha |
title_short | Melatonin Rescued Reactive Oxygen Species-Impaired Osteogenesis of Human Bone Marrow Mesenchymal Stem Cells in the Presence of Tumor Necrosis Factor-Alpha |
title_sort | melatonin rescued reactive oxygen species impaired osteogenesis of human bone marrow mesenchymal stem cells in the presence of tumor necrosis factor alpha |
url | http://dx.doi.org/10.1155/2019/6403967 |
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