IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling
IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling
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DOI：
10.1038/cdd.2009.74
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发表时间：
2009-10-01
影响因子：
12.4
通讯作者：
Kim, H-H
中科院分区：
文献类型：
--
作者：
Huang, H.;Kim, H. J.;Kim, H-H
白细胞介素-17（IL-17）是主要由TH-17细胞分泌的细胞因子。虽然IL-17主要与组织炎症的诱导相关，但IL-17的其他生物学作用，包括非免疫功能，尚未得到彻底的探索。在这里，我们报告说，T细胞产生的IL-17可以诱导人骨髓间充质干细胞（hMSCs）的增殖的方式依赖于活性氧（ROS）的产生。Rac 1 GT3和NADPH氧化酶1（Nox 1）被IL-17激活以产生ROS，这反过来刺激hMSC增殖。MEK-ERK通路的激活对于IL-17依赖性hMSC增殖也是至关重要的。TRAF 6和Act 1是激活Nox 1和磷酸化MEK对IL-17刺激所必需的。有趣的是，IL-17不仅加速hMSCs的增殖，而且还诱导其迁移、运动和成骨细胞分化。此外，IL-17诱导hMSC上的M-CSF和NF-κ B配体（RANKL）的受体活化剂的表达，从而在体内和体外支持破骨细胞生成。在这些结果的基础上，我们认为IL-17可以作为一个信号，通过调节hMSC的募集，增殖，运动和分化诱导广泛的骨转换。
Interleukin-17 (IL-17) is a cytokine secreted primarily by TH-17 cells. Although IL-17 is primarily associated with the induction of tissue inflammation, the other biological roles of IL-17, including non-immune functions, have yet to be thoroughly explored. Here, we report that T-cell-produced IL-17 can induce proliferation of human bone marrow-derived mesenchymal stem cells (hMSCs) in a manner dependent on the generation of reactive oxygen species (ROS). Rac1 GTPase and NADPH oxidase 1 (Nox1) are activated by IL-17 to produce ROS, which in turn stimulates hMSC proliferation. The activation of the MEK-ERK pathway is also crucial for IL-17-dependent hMSC proliferation. TRAF6 and Act1 are required to activate Nox 1 and to phosphorylate MEK on IL-17 stimulation. Interestingly, IL-17 not only accelerates the proliferation of hMSCs, but also induces their migration, motility, and osteoblastic differentiation. Furthermore, IL-17 induces the expression of M-CSF and receptor activator of NF-kappa B ligand (RANKL) on hMSCs, thereby supporting osteoclastogenesis both in vivo and in vitro. On the basis of these results, we suggest that IL-17 can function as a signal to induce extensive bone turnover by regulating hMSC recruitment, proliferation, motility, and differentiation.