Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China (mainland).
Jindian Dendure Chain Group, Chengdu, Sichuan, China (mainland).
Med Sci Monit. 2017 Aug 24;23:4095-4101. doi: 10.12659/msm.903027.
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.
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。
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。
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。