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Title: Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin

Abstract

The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis (RA), particularly bone loss, have not been clearly explored. The imbalance between osteoblasts and osteoclasts is a major reason for bone loss. The dysfunction of osteoblasts, which are derived from mesenchymal stem cells (MSCs), induced bone erosion occurs earlier and is characterized as more insidious. Here, we showed that the nuclear expression and translocation of Ahr were both significantly increased in MSCs from collagen-induced arthritis (CIA) mice. The enhanced Ahr suppressed the mRNA levels of osteoblastic markers including Alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2) in the differentiation of MSCs to osteoblasts in CIA. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated activation of Ahr dose-dependently suppressed the expression of osteoblastic markers. In addition, the expression of β-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited β-catenin expression. The Wnt3a-induced the activation of Wnt/β-catenin pathway partly rescued the osteogenesis decline induced by TCDD. Taken together, these results indicate that activated Ahr plays a negative role in CIA MSCs osteogenesis, possibly by suppressing the expression of β-catenin. - Highlights: • The Ahr pathway displays an activated profile in CIAmore » MSCs. • The activation of Ahr suppresses osteogenesis in CIA MSCs. • TCDD suppresses osteogenesis in a dose-dependent manner. • The activation of Ahr inhibits β-catenin expression to exacerbate bone erosion.« less

Authors:
 [1];  [1];  [2]; ; ; ;  [1];  [3];  [1];  [1];  [1]
  1. Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069 (China)
  2. (China)
  3. Department of Clinical Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu Province 730000 (China)
Publication Date:
OSTI Identifier:
22649815
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 350; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKALINE PHOSPHATASE; AROMATICS; CARBOXYLIC ACIDS; COLLAGEN; CONNECTIVE TISSUE CELLS; DIOXIN; INHIBITION; MESSENGER-RNA; MICE; PATHOGENESIS; PYRAZOLES; RECEPTORS; RHEUMATIC DISEASES; SKELETON; STEM CELLS; TRANSCRIPTION; TRANSCRIPTION FACTORS; TRANSLOCATION

Citation Formats

Tong, Yulong, Niu, Menglin, Department of Blood Transfusion, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing 100142, Du, Yuxuan, Mei, Wentong, Cao, Wei, Dou, Yunpeng, Yu, Haitao, Du, Xiaonan, Yuan, Huihui, E-mail: huihui_yuan@163.com, and Zhao, Wenming, E-mail: zhao-wenming@163.com. Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2016.12.009.
Tong, Yulong, Niu, Menglin, Department of Blood Transfusion, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing 100142, Du, Yuxuan, Mei, Wentong, Cao, Wei, Dou, Yunpeng, Yu, Haitao, Du, Xiaonan, Yuan, Huihui, E-mail: huihui_yuan@163.com, & Zhao, Wenming, E-mail: zhao-wenming@163.com. Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin. United States. doi:10.1016/J.YEXCR.2016.12.009.
Tong, Yulong, Niu, Menglin, Department of Blood Transfusion, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing 100142, Du, Yuxuan, Mei, Wentong, Cao, Wei, Dou, Yunpeng, Yu, Haitao, Du, Xiaonan, Yuan, Huihui, E-mail: huihui_yuan@163.com, and Zhao, Wenming, E-mail: zhao-wenming@163.com. Sun . "Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin". United States. doi:10.1016/J.YEXCR.2016.12.009.
@article{osti_22649815,
title = {Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of β-catenin},
author = {Tong, Yulong and Niu, Menglin and Department of Blood Transfusion, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing 100142 and Du, Yuxuan and Mei, Wentong and Cao, Wei and Dou, Yunpeng and Yu, Haitao and Du, Xiaonan and Yuan, Huihui, E-mail: huihui_yuan@163.com and Zhao, Wenming, E-mail: zhao-wenming@163.com},
abstractNote = {The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis (RA), particularly bone loss, have not been clearly explored. The imbalance between osteoblasts and osteoclasts is a major reason for bone loss. The dysfunction of osteoblasts, which are derived from mesenchymal stem cells (MSCs), induced bone erosion occurs earlier and is characterized as more insidious. Here, we showed that the nuclear expression and translocation of Ahr were both significantly increased in MSCs from collagen-induced arthritis (CIA) mice. The enhanced Ahr suppressed the mRNA levels of osteoblastic markers including Alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2) in the differentiation of MSCs to osteoblasts in CIA. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated activation of Ahr dose-dependently suppressed the expression of osteoblastic markers. In addition, the expression of β-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited β-catenin expression. The Wnt3a-induced the activation of Wnt/β-catenin pathway partly rescued the osteogenesis decline induced by TCDD. Taken together, these results indicate that activated Ahr plays a negative role in CIA MSCs osteogenesis, possibly by suppressing the expression of β-catenin. - Highlights: • The Ahr pathway displays an activated profile in CIA MSCs. • The activation of Ahr suppresses osteogenesis in CIA MSCs. • TCDD suppresses osteogenesis in a dose-dependent manner. • The activation of Ahr inhibits β-catenin expression to exacerbate bone erosion.},
doi = {10.1016/J.YEXCR.2016.12.009},
journal = {Experimental Cell Research},
number = 2,
volume = 350,
place = {United States},
year = {Sun Jan 15 00:00:00 EST 2017},
month = {Sun Jan 15 00:00:00 EST 2017}
}