Dysregulation of the miR-146a-Smad4 axis impairs osteogenesis of bone mesenchymal stem cells under inflammation

Wei Kuang; Liwei Zheng; Xin Xu; Yao Lin; Jiong Lin; Jiahua Wu; Jiali Tan

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Dysregulation of the miR-146a-Smad4 axis impairs osteogenesis of bone mesenchymal stem cells under inflammation

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摘要

Osteoporosis is a common disease that affects patient quality of life, especially among the elderly population.Although inflammation contributes significantly to osteoporosis, the underlying mechanism is unclear. In this study, we found that tumor necrosis factor(TNF)-α, an inflammatory environment mimic, inhibits osteogenesis of bone mesenchymal stem cells(BMSCs), induces mi R-146 a and decreases Smad4. Moreover,overexpression of mi R-146 a inhibited the osteogenic ability of BMSCs, whereas blocking mi R-146 a partially rescued the osteogenesis deficiency under TNF-α treatment. Molecularly, mi R-146 a decreased Smad4 expression at the protein level by binding to an element located in the Smad4 30-untranslated region, and restoration of Smad4 reversed the inhibitory effects of mi R-146 a on osteogenesis. Together, our results showed that the inflammatory environment mimic TNF-α inhibits osteogenesis via upregulation of mi R-146 a and subsequent downregulation of Smad4, thus suggesting that therapeutic manipulation of mi R-146 a maybe a potential strategy to improve osteogenesis in the context of osteoporosis.

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《骨研究：英文》 |2017年第004期|P.375-383|共9页
作者
Wei Kuang; Liwei Zheng; Xin Xu; Yao Lin; Jiong Lin; Jiahua Wu; Jiali Tan;
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作者单位

[1]Department of Stomatology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China;

[2]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China;

[2]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China;

[3]Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhau, China;

[3]Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhau, China;

[3]Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhau, China;

[3]Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhau, China;

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正文语种 CHI
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关键词
Dysregulation; miR-146a-Smad4; axis; bone; mesenchymal; stem;

机译：调节异常;miR-146a-Smad4;轴;骨;间质;干;

Dysregulation of the miR-146a-Smad4 axis impairs osteogenesis of bone mesenchymal stem cells under inflammation

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