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白细胞介素-17A 通过 Wnt 信号通路抑制骨髓间充质干细胞的成骨分化。

IL-17A Inhibits Osteogenic Differentiation of Bone Mesenchymal Stem Cells via Wnt Signaling Pathway.

机构信息

Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland).

Jindian Dendure Chain Group, Chengdu, Sichuan, China (mainland).

出版信息

Med Sci Monit. 2017 Aug 24;23:4095-4101. doi: 10.12659/msm.903027.

Abstract

BACKGROUND Interleukin-17A (IL-17A) is not only an important modulator of inflammatory reactions, but also affects bone metabolism, which is involved in osteogenic differentiation of stem cells. However, the role and mechanism of IL-17A in osteogenic differentiation of bone mesenchymal stem cells (BMSCs) are not fully understood. In this study, we investigated the role and mechanism of IL-17A in osteogenic differentiation of BMSCs. MATERIAL AND METHODS The osteogenic differentiation of BMSCs was induced by osteoblast-induction medium with IL-17A or without IL-17A. The osteogenic differentiation of BMSCs was confirmed by the alkaline phosphatase and alizarin red staining. The lentiviral plasmid was used to construct the sFRP1-shRNA expression vector. The associated osteogenic differentiation marks (RUNX2, ALP, OPN), Wnt signaling pathway inhibitor (sFRP1), and modulators of Wnt signaling pathway (Wnt3, Wnt6) were detected by qRT-PCR and Western blot method. RESULTS The results showed that the addition of IL-17A inhibited osteogenic differentiation of BMSCs. IL-17A induced up-regulated expression of sFRP1 and down-regulated expression of Wnt3 and Wnt6 in BMSCs. In addition, sFRP1-shRNA abolished the inhibition effect of IL-17A in osteogenic differentiation of BMSCs and induced up-regulated expression of Wnt3 and Wnt6 in the Wnt signaling pathway in BMSCs. CONCLUSIONS Our findings show that IL-17A inhibits osteogenic differentiation of bone mesenchymal stem cells via the Wnt signaling pathway.

摘要

背景

白细胞介素-17A(IL-17A)不仅是炎症反应的重要调节剂,还影响骨代谢,参与干细胞的成骨分化。然而,IL-17A 在骨髓间充质干细胞(BMSCs)成骨分化中的作用和机制尚不完全清楚。在这项研究中,我们研究了 IL-17A 在 BMSCs 成骨分化中的作用和机制。

材料和方法

用含或不含 IL-17A 的成骨诱导培养基诱导 BMSCs 的成骨分化。通过碱性磷酸酶和茜素红染色来确认 BMSCs 的成骨分化。利用慢病毒质粒构建 sFRP1-shRNA 表达载体。通过 qRT-PCR 和 Western blot 方法检测相关成骨分化标志物(RUNX2、ALP、OPN)、Wnt 信号通路抑制剂(sFRP1)和 Wnt 信号通路调节剂(Wnt3、Wnt6)。

结果

结果表明,添加 IL-17A 抑制 BMSCs 的成骨分化。IL-17A 诱导 BMSCs 中 sFRP1 的表达上调,Wnt3 和 Wnt6 的表达下调。此外,sFRP1-shRNA 消除了 IL-17A 对 BMSCs 成骨分化的抑制作用,并诱导 Wnt 信号通路中 BMSCs 中 Wnt3 和 Wnt6 的表达上调。

结论

我们的研究结果表明,IL-17A 通过 Wnt 信号通路抑制骨髓间充质干细胞的成骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/109a/5580517/51c1bc3ebcfb/medscimonit-23-4095-g001.jpg

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