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LNGFR 靶向 Wnt/β-catenin 通路并促进大鼠中胚层干细胞的成骨分化。

LNGFR targets the Wnt/β-catenin pathway and promotes the osteogenic differentiation in rat ectomesenchymal stem cells.

机构信息

Department of Stomatology, Daping Hospital, Research Institute of Field Surgery, Third Military Medical University, Chongqing, 400042, China.

Department of Periodontology, Stomatological Hospital, Zunyi Medical College, Zunyi, Guizhou, 563003, China.

出版信息

Sci Rep. 2017 Sep 8;7(1):11021. doi: 10.1038/s41598-017-11555-9.

Abstract

Considerable evidence has shown that the Wnt/β-catenin pathway is involved in osteogenic differentiation in various stem cells. However, the role of Wnt/β-catenin pathway in regulating the osteogenic differentiation of rat ectomesenchymal stem cells (EMSCs), which are considered to be the progenitors of dental mesenchymal stem cells, remains unknown. In this study, we demonstrated that nuclear β-catenin was upregulated during EMSC osteogenic differentiation. The Wnt signalling inhibitor IWR-1-endo inhibited EMSC osteogenic differentiation, while the Wnt signalling agonist SKL2001 promoted it. Moreover, nuclear β-catenin was further upregulated by the overexpression of low-affinity nerve growth factor receptor (LNGFR) during EMSC osteogenic differentiation. Further experiments demonstrated that LNGFR overexpression enhanced EMSC osteogenic differentiation, while LNGFR silencing decreased it. Additionally, IWR-1-endo attenuated LNGFR-enhanced EMSC osteogenic differentiation. Collectively, our data reveal that LNGFR targets the Wnt/β-catenin pathway and positively regulates EMSC osteogenic differentiation, suggesting that Wnt/β-catenin pathway may be involved in the development of teeth and that the targeting Wnt/β-catenin pathway may have great potential for applications in dental tissue engineering regeneration.

摘要

大量证据表明,Wnt/β-catenin 通路参与了各种干细胞的成骨分化。然而,Wnt/β-catenin 通路在调节大鼠外胚间充质干细胞(EMSCs)的成骨分化中的作用尚不清楚,而这些细胞被认为是牙间充质干细胞的前体细胞。在本研究中,我们证明了核β-catenin 在 EMSC 成骨分化过程中上调。Wnt 信号抑制剂 IWR-1-endo 抑制 EMSC 成骨分化,而 Wnt 信号激动剂 SKL2001 则促进其分化。此外,在 EMSC 成骨分化过程中,低亲和力神经生长因子受体(LNGFR)的过表达进一步上调了核β-catenin。进一步的实验表明,LNGFR 的过表达增强了 EMSC 的成骨分化,而 LNGFR 的沉默则降低了这一作用。此外,IWR-1-endo 减弱了 LNGFR 增强的 EMSC 成骨分化。总之,我们的数据揭示了 LNGFR 靶向 Wnt/β-catenin 通路并正向调节 EMSC 成骨分化,这表明 Wnt/β-catenin 通路可能参与了牙齿的发育,靶向 Wnt/β-catenin 通路在牙组织工程再生中可能具有很大的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc1a/5591262/fcf1765a4879/41598_2017_11555_Fig1_HTML.jpg

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