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.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China; Department of Blood Transfusion, Peking University Cancer Hospital & Institute, No. 52 Fucheng Rd., Beijing 100142, PR China.
authors.forename: Menglin
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors.forename: Wentong
authors.initials: W
authors.lastname: Mei
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Department of Clinical Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu Province 730000, PR China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China. Electronic address: huihui_yuan@163.com.
authors.forename: Huihui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, PR China. Electronic address: zhao-wenming@163.com.
authors.forename: Wenming
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C493716:Runx2 protein, mouse; D051176:beta Catenin; D000469:Alkaline Phosphatase
keywords: Aryl hydrocarbon receptor (Ahr); Collagen-induced arthritis (CIA); Differentiation; Mesenchymal stem cell (MSC); Osteogenesis; β-catenin