TNF-α inhibits SATB2 expression and osteoblast differentiation through NF-κB and MAPK pathways
| Autor: | Xiaoying Zhao, Ning Zhang, Jiake Xu, Guoli Hu, Yu Shi, Wen Wu, Chuandong Wang, Xiaoling Zhang, Chijian Zuo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway SATB2 inhibition inflammation-induced bone loss Chemistry p38 mitogen-activated protein kinases Osteoblast Bone resorption Cell biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Oncology Osteoclast TNF-α osteoblast differentiation medicine Tumor necrosis factor alpha Signal transduction C2C12 Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.23373 |
| Popis: | Although the mechanisms of Tumor necrosis factor alpha (TNF-α) on facilitating osteoclast differentiation and bone resorption is well known, the mechanisms behind the suppression of the osteoblast differentiation from mesenchymal stem cells (MSCs) are still poorly understood. In this study, we observed a negative correlation between TNF-α levels and the expression of special AT-rich sequence-binding protein 2 (SATB2), a critical osteoblastogenesis transcription factor, in ovariectomy (OVX)-induced bone loss and IL-1-induced arthritis animal model. We found that TNF-α treatment inhibited mesenchymal cell line C2C12 osteoblast differentiation and sharply decreased BMP2-induced SATB2 expression. Upon TNF-α treatment, the activity of smad1/5/8 was inhibited, by contrast, extracellular signal-regulated kinase-1/2 (ERK1/2) and P38 was increased in C2C12 cells, the inhibitor of ERK1/2 (U0126) was found to abrogate the TNF-α inhibition of SATB2 expression. Furthermore, the NF-κB signaling pathway in C2C12 cells was significantly activated by the treatment of TNF-α, and TNF-α induced NF-κB directly binds to SATB2 promoter to suppress its expression. These results suggest that TNF-α suppresses SATB2 expression through activating NF-κB and MAPK signaling and depressing smad1/5/8 signaling, which contributes to the inhibition of osteoblast differentiation and might be potential therapeutic targets for inflammation-induced bone loss. |
| Databáze: | OpenAIRE |
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