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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Main Authors: Xianjian Qiu, Xudong Wang, Jincheng Qiu, Yuanxin Zhu, Tongzhou Liang, Bo Gao, Zizhao Wu, Chengjie Lian, Yan Peng, Anjing Liang, Peiqiang Su, Dongsheng Huang
Format: Article
Language:English
Published: Wiley 2019-01-01
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.
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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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