TNF-α inhibits SATB2 expression and osteoblast differentiation through NF-κB and MAPK pathways.

Autor:	Zuo C; Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.; The Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China., Zhao X; Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China., Shi Y; The Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China., Wu W; Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China., Zhang N; The Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China., Xu J; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia 6009, Australia., Wang C; Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China., Hu G; Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China., Zhang X; Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.; The Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Dec 18; Vol. 9 (4), pp. 4833-4850. Date of Electronic Publication: 2017 Dec 18 (Print Publication: 2018).
DOI:	10.18632/oncotarget.23373
Abstrakt:	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. Competing Interests: CONFLICTS OF INTEREST The authors have declared that no conflicts of interest exists.
Databáze:	MEDLINE
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