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miR-203-3p 通过靶向 Smad1 参与抑制颌骨中的糖尿病相关成骨作用。

miR‑203‑3p participates in the suppression of diabetes‑associated osteogenesis in the jaw bone through targeting Smad1.

机构信息

Department of Endodontics, The Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, P.R. China.

Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, The Affiliated Stomatology Hospital, Chongqing Medical University, Chongqing 401147, P.R. China.

出版信息

Int J Mol Med. 2018 Mar;41(3):1595-1607. doi: 10.3892/ijmm.2018.3373. Epub 2018 Jan 9.

Abstract

Certain microRNAs (miRs) have important roles in the maintenance of bone development and metabolism, and a variety of miRs are known to be deregulated in diabetes. The present study investigated the role of miR‑203‑3p in the regulation of bone loss by assessing jaw bones of a rat model of type 2 diabetes. The results indicated that miR‑203‑3p inhibited osteogenesis in the jaws of diabetic rats and in rat bone marrow mesenchymal stem cells cultured in high‑glucose medium. A luciferase re-porter assay was used to verify the bioinformatics prediction that miR‑203‑3p targets the 3'‑untranslated region of Smad1, which is an important mediator of the bone morphogenetic protein (BMP)/Smad pathway. Overexpression of Smad1 attenuated the miR‑203‑3p‑mediated suppres-sion of osteogenic differentiation. It was therefore indicated that the BMP/Smad pathway is attenuated and the transforming growth factor‑β/activin pathway is promoted by Smad1 reduction. Taken together, it was indicated that miR‑203‑3p inhibits osteogenesis in jaw bones of diabetic rats by targeting Smad1 to inhibit the BMP/Smad pathway.

摘要

某些 microRNAs(miRs)在维持骨骼发育和代谢方面发挥着重要作用,已知多种 miR 在糖尿病中失调。本研究通过评估 2 型糖尿病大鼠模型的颌骨,研究了 miR-203-3p 在调节骨丢失中的作用。结果表明,miR-203-3p 抑制了糖尿病大鼠颌骨和高糖培养基中培养的大鼠骨髓间充质干细胞的成骨作用。荧光素酶报告基因检测验证了生物信息学预测,即 miR-203-3p 靶向骨形态发生蛋白(BMP)/Smad 通路的重要介质 Smad1 的 3'非翻译区。Smad1 的过表达减弱了 miR-203-3p 介导的成骨分化抑制作用。因此,表明 Smad1 的减少减弱了 BMP/Smad 通路,促进了转化生长因子-β/激活素通路。综上所述,miR-203-3p 通过靶向 Smad1 抑制 BMP/Smad 通路来抑制糖尿病大鼠颌骨中的成骨作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c77/5819914/0799e1eb3ca6/IJMM-41-03-1595-g00.jpg

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