Combination of Interleukin-27 and MicroRNA for Enhancing Expression of Anti-Inflammatory and Proosteogenic Genes.
Combination of Interleukin-27 and MicroRNA for Enhancing Expression of Anti-Inflammatory and Proosteogenic Genes.
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DOI：
10.1155/2017/6365857
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Figueiredo ML
中科院分区：
文献类型：
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作者：
Figueiredo Neto M;Figueiredo ML
炎症或类风湿性关节炎(RA)的炎症缓解已成为一个可实现的目标；然而，在许多患者中，骨侵蚀仍在继续。白介素27调节免疫和骨细胞平衡，也抑制类风湿关节炎中几种炎性细胞的活性。尽管有希望，但IL-27临床翻译的挑战一直是它在体内的部分作用。由于它们能够调节骨骼的可塑性和免疫细胞分化，我们研究了几种microRNA(MiR)候选分子在增强IL-27效应方面的潜力。利用分化、荧光素酶和实时定量聚合酶链式反应分析，我们发现IL-27促进成骨细胞分化，减少成骨细胞抑制基因的表达，减少破骨细胞分化，结果提示与转化生长因子β/骨形态发生蛋白/SMAD和JAK/STAT通路有潜在的协同作用。我们选择了这些途径和相关途径的miRNA调节剂，以检查IL-27的作用是否可以被增强用于治疗应用。MiR-29b和miR-21增强IL-27前成骨作用，同时下调破骨细胞信号，也致力于减少激活的巨噬细胞中的炎症信号，而miR-21和miR-20b与IL-27共同作用，减少成纤维细胞和T细胞中炎症基因的表达。似乎有几个miRNAs可以用来增强IL-27‘S在调节成骨和减少促炎信号方面的作用。
Remission of inflammation has become an achievable goal in inflammatory or rheumatoid arthritis (RA); however, bone erosion continues in many patients. Interleukin- (IL-) 27 regulates immune and bone cell balance and also suppresses activities of several inflammatory cell types in RA. Despite its promise, challenges to clinical translation of IL-27 have been its partial effects in vivo. Due to their ability to modulate plasticity of bone and immune cell differentiation, we examined the potential for several microRNA (miR) candidates in enhancing the effects of IL-27. Using differentiation, luciferase, and real time quantitative PCR assays, we show that IL-27 promotes osteoblast differentiation, reduces expression of osteoblast inhibitory genes, and reduces osteoclast differentiation, and results suggest a potential coordination with TGFβ/BMP/SMAD and JAK/STAT pathways. We selected miRNA regulators of these and related pathways to examine whether the effects of IL-27 could be augmented for therapeutic applications. miR-29b and miR-21 augmented IL-27 proosteogenic while downregulating osteoclastogenic signals and also worked to reduce inflammatory signaling in activated macrophages, while miR-21 and miR-20b worked with IL-27 to reduce inflammatory gene expression in fibroblasts and T cells. It appears that several miRNAs can be utilized to enhance IL-27's impact on modulating osteogenesis and reducing proinflammatory signaling.