Title | Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collagen-induced arthritic mice through the inhibition of beta-catenin |
Authors | Tong, Yulong Niu, Menglin Du, Yuxuan Mei, Wentong Cao, Wei Dou, Yunpeng Yu, Haitao Du, Xiaonan Yuan, Huihui Zhao, Wenming |
Affiliation | Capital Med Univ, Sch Basic Med Sci, Dept Immunol, 10 Xitoutiao, Beijing 100069, Peoples R China. Peking Univ, Canc Hosp & Inst, Dept Blood Transfus, 52 Fucheng Rd, Beijing 100142, Peoples R China. Lanzhou Univ, Hosp 1, Dept Clin Lab, Lanzhou 730000, Gansu, Peoples R China. |
Keywords | Aryl hydrocarbon receptor (Ahr) Collagen-induced arthritis (CIA) Mesenchymal stem cell (MSC) Differentiation Osteogenesis beta-catenin RHEUMATOID-ARTHRITIS IN-VITRO OSTEOBLAST DIFFERENTIATION SIGNALING PATHWAY BONE EROSION CANCER CELLS ACTIVATION PROLIFERATION EXPRESSION DISEASE |
Issue Date | 2017 |
Publisher | EXPERIMENTAL CELL RESEARCH |
Citation | EXPERIMENTAL CELL RESEARCH.2017,350(2),349-357. |
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 beta-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited beta-catenin expression. The Wnt3a-induced the activation of Wnt/beta-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 beta-catenin. |
URI | http://hdl.handle.net/20.500.11897/475687 |
ISSN | 0014-4827 |
DOI | 10.1016/j.yexcr.2016.12.009 |
Indexed | SCI(E) |
Appears in Collections: | 北京肿瘤医院 |