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IL-17 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes

机译:IL-17改变了间充质干细胞利基对骨的合作骨细胞

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Bone remodeling is a strictly regulated dynamic process that cycles between bone formation and resorption, and interleukin-17 (IL-17) critically orchestrates the activation and differentiation of both osteoblasts and osteoclasts. Mesenchymal stem cells (MSCs) within their native environment receive biochemical stimuli from surrounding cells that influences their differentiation into bone precursors, while the roles of osteocytes in regulating the osteogenic differentiation of MSCs remain unclear. This study investigated the specific roles of IL-17 signaling cascades and osteocyte-specific pathways in the osteogenesis of MSCs. Using a transwell coculture (CC) system, we explored the effects of osteocytes and osteoblasts on the osteogenesis of MSCs with and without IL-17 supplementation. A polycaprolactone (PCL) three-dimensional (3D) culture model was used to evaluate their osteogenic potential in the presence of osteocytes and IL-17. Notably, IL-17 induced osteogenesis in MSCs, which could be attenuated by blocking IL-17 receptor A. The osteogenic differentiation of MSCs promoted by IL-17 was further enhanced by CC with osteocytes. Moreover, proinflammatory cytokines IL-6 and IL-1β played an important role in IL-17-dependent differentiation, via the phosphorylation of AKT, signal transducer and activator of transcription 3, and extracellular signal-regulated kinase 1/2 signaling pathways in the MSC niche. The present study confirms a synergistic effect of osteocytes and IL-17 in the production of biochemical signals to stimulate the osteogenic differentiation of MSCs, which could be further promoted in the PCL 3D-scaffold. These findings provide important insight into the mechanisms of MSCs activation and osteogenic differentiation within the native stem cell niche, and suggest a possible role of IL-17 in bone tissue engineering.
机译:骨重建是一个严格监管动态与骨形成过程,周期吸收,interleukin-17 IL-17批判性协调激活和分化成骨细胞和破骨细胞。干细胞(msc)在其原生环境从周围获得生化刺激细胞影响其分化骨前体细胞,而骨细胞的作用调控msc的成骨分化尚不清楚。特定角色IL-17信号级联osteocyte-specific骨生成的途径msc。我们研究了骨细胞的影响成骨细胞在骨与和msc没有IL-17补充。(PCL)三维(3 d)文化模型用于评估其成骨的潜力骨细胞的存在和IL-17。msc IL-17诱导骨生成,被阻塞IL-17受体a减毒成骨分化的msc提升IL-17被CC与骨细胞进一步加强。此外,促炎细胞因子il - 6和il - 1β在IL-17-dependent发挥了重要的作用分化,通过一种蛋白激酶的磷酸化,信号传感器和转录的激活3,细胞外signal-regulated激酶1/2信号通路在MSC。研究证实骨细胞的协同效应和IL-17生产生化刺激成骨的信号msc分化,这可能会进一步促进了PCL 3 d-scaffold。的机制提供重要的见解msc激活和成骨分化在本机干细胞利基,并建议可能的IL-17在骨组织中的作用工程。

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