Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α

Objective. To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods. CIA mice were divided into...

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Main Authors: Chang Liu, Huayong Zhang, Xiaojun Tang, Ruihai Feng, Genhong Yao, Weiwei Chen, Wenchao Li, Jun Liang, Xuebing Feng, Lingyun Sun
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/4069032
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author Chang Liu
Huayong Zhang
Xiaojun Tang
Ruihai Feng
Genhong Yao
Weiwei Chen
Wenchao Li
Jun Liang
Xuebing Feng
Lingyun Sun
author_facet Chang Liu
Huayong Zhang
Xiaojun Tang
Ruihai Feng
Genhong Yao
Weiwei Chen
Wenchao Li
Jun Liang
Xuebing Feng
Lingyun Sun
author_sort Chang Liu
collection DOAJ
description Objective. To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods. CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the bone morphology parameters. Osteogenic differentiation of treated CIA mice was determined. Bone marrow mesenchymal stem cells (BM-MSCs) from CIA mice were treated with TNF-α in vitro to explore their effects on osteogenesis. Results. The arthritis score was significantly reduced in the UC-MSC transplantation and anti-TNF-α-treated CIA groups, compared with control mice (P<0.001). Micro-CT showed that CIA mice developed osteoporosis at 12 weeks after immunization. The bone morphology parameters were partially improved in UC-MSC-treated CIA mice. Impaired osteogenic differentiation functions were indicated by decreased ALP activity (P<0.001) and reduced mRNA and protein levels of osteogenic marker genes (P<0.05) in CIA mice compared with DBA/1 mice. UC-MSC treatment significantly upregulated the impaired osteogenic differentiation ability in CIA mice. Meanwhile, the serum TNF-α level was decreased significantly in the UC-MSC group. The osteogenesis was reduced with the addition of TNF-α in vitro. Conclusion. This study demonstrated that UC-MSC transplantation not only significantly improved the joint damage but also played a beneficial role in osteoporosis in CIA mice. Mechanistically, the improved osteogenic differentiation of CIA under UC-MSC treatment may be achieved by inhibition of TNF-α.
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spelling doaj-art-4b441af23cc54bd2bef799a3c12070282025-08-20T03:36:26ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/40690324069032Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-αChang Liu0Huayong Zhang1Xiaojun Tang2Ruihai Feng3Genhong Yao4Weiwei Chen5Wenchao Li6Jun Liang7Xuebing Feng8Lingyun Sun9Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaDepartment of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, ChinaObjective. To investigate the effects of umbilical cord mesenchymal stem cell (UC-MSC) transplantation on joint damage and osteoporosis in collagen-induced arthritis (CIA) mice and to explore the mechanisms by which UC-MSCs modulate the osteogenic differentiation. Methods. CIA mice were divided into the following treated groups: UC-MSC transplantation group, antitumor necrosis factor- (TNF-) α group, and zoledronic acid (ZA) group. Microcomputed tomography (micro-CT) was used to analyze the bone morphology parameters. Osteogenic differentiation of treated CIA mice was determined. Bone marrow mesenchymal stem cells (BM-MSCs) from CIA mice were treated with TNF-α in vitro to explore their effects on osteogenesis. Results. The arthritis score was significantly reduced in the UC-MSC transplantation and anti-TNF-α-treated CIA groups, compared with control mice (P<0.001). Micro-CT showed that CIA mice developed osteoporosis at 12 weeks after immunization. The bone morphology parameters were partially improved in UC-MSC-treated CIA mice. Impaired osteogenic differentiation functions were indicated by decreased ALP activity (P<0.001) and reduced mRNA and protein levels of osteogenic marker genes (P<0.05) in CIA mice compared with DBA/1 mice. UC-MSC treatment significantly upregulated the impaired osteogenic differentiation ability in CIA mice. Meanwhile, the serum TNF-α level was decreased significantly in the UC-MSC group. The osteogenesis was reduced with the addition of TNF-α in vitro. Conclusion. This study demonstrated that UC-MSC transplantation not only significantly improved the joint damage but also played a beneficial role in osteoporosis in CIA mice. Mechanistically, the improved osteogenic differentiation of CIA under UC-MSC treatment may be achieved by inhibition of TNF-α.http://dx.doi.org/10.1155/2018/4069032
spellingShingle Chang Liu
Huayong Zhang
Xiaojun Tang
Ruihai Feng
Genhong Yao
Weiwei Chen
Wenchao Li
Jun Liang
Xuebing Feng
Lingyun Sun
Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α
Stem Cells International
title Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α
title_full Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α
title_fullStr Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α
title_full_unstemmed Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α
title_short Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α
title_sort mesenchymal stem cells promote the osteogenesis in collagen induced arthritic mice through the inhibition of tnf α
url http://dx.doi.org/10.1155/2018/4069032
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