Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies
Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies
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DOI：
10.1093/rheumatology/kew384
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发表时间：
2017-03-01
期刊：
影响因子：
5.5
通讯作者：
McGonagle, Dennis
中科院分区：
文献类型：
--
作者：
El-Zayadi, Ahmed A.;Jones, Elena A.;McGonagle, Dennis
目标。 SpA 在遗传和治疗上与 IL-23 相关，IL-23 反过来调节 IL-22，这是一种与实验模型中新骨形成调节有关的细胞因子。我们假设 IL-22 作为其他生态位干细胞的主要调节因子，也可能调节人间充质干细胞 (MSC) 成骨。方法。在存在或不存在 IFN-γ 和 TNF 的情况下评估 IL-22 对体外 MSC 增殖、迁移和成骨分化的影响（以确定促炎环境中的 IL-22 活性）。使用比色 XTT 测定、跨孔迁移测定、MSC 谱系标记的定量实时 PCR (qRT-PCR) 和成骨测定。结果。用 IL-22、IFN-γ 和 TNF 联合处理 MSC 导致 MSC 增殖 (P = 0.008) 和迁移 (P = 0.04) 增加，这种效果在单独用 IL-22 处理的细胞和未处理的细胞中未见。单独使用 IL-22 可以上调成骨和脂肪形成转录因子，但不能上调软骨形成转录因子（P < 0.05）。 IL-22 暴露后 MSC 成骨作用增强（P = 0.03，通过钙生成测量）。 IFN-γ 和 TNF 联合或不联合 IL-22 抑制 MSC 成骨（P = 0.03）。结论。这项工作表明，IL-22 参与炎症环境中的人 MSC 增殖/迁移，而 MSC 成骨仅在没有 IFN-γ/TNF 的情况下发生。 IL-22 对 MSC 功能的这些影响是探索人类 SpA 病理性炎症后成骨的新途径。
Objectives. The SpAs are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesize that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis.Methods. The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-gamma and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real-time PCR (qRT-PCR) for MSC lineage markers and osteogenesis assays were used.Results. Combined treatment of MSC with IL-22, IFN-gamma and TNF resulted in increased MSC proliferation (P = 0.008) and migration (P = 0.04), an effect that was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic and adipogenic, but not chondrogenic, transcription factors were upregulated by IL-22 alone (P< 0.05). MSC osteogenesis was enhanced following IL-22 exposure (P = 0.03, measured by calcium production). The combination of IFN-gamma and TNF with or without IL-22 suppressed MSC osteogenesis (P = 0.03).Conclusion. This work shows that IL-22 is involved in human MSC proliferation/migration in inflammatory environments, with MSC osteogenesis occurring only in the absence of IFN-gamma/TNF. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA.