Il-6 signaling exacerbates hallmarks of tendon lesions by stimulating progenitor proliferation & migration to damage.

We leveraged an explant-based, tissue engineered model of tendon damage to study cross-compartmental interactions between the tendon core and extrinsic progenitors, as well as between the tendon core and extrinsic macrophages. We suspected IL-6 signaling to play a major role in this crosstalk, so we also incorporated core explants from IL-6 knock-out mice. Overall design: 1) Comparative gene expression profiling analysis of RNA-seq data for wildtype core explants or IL-6 knock-out core explants surrounded by a cell-free hydrogel, one filled with extrinsic progenitors, or one filled with macrophages. 2) Comparative gene expression profiling analysis of RNA-seq data for extrinsic progenitors surrounding a wildtype or a knock-out core.

本研究利用基于外植体（explant）的肌腱损伤组织工程模型，探究肌腱核心区与外源性祖细胞，以及肌腱核心区与外源性巨噬细胞之间的跨室互作调控机制。我们推测白细胞介素6（IL-6）信号通路在该互作中发挥核心调控作用，因此同时纳入了来自IL-6敲除小鼠的肌腱核心外植体样本。整体实验设计如下：1）针对野生型或IL-6敲除型肌腱核心外植体的RNA测序（RNA-seq）数据开展比较基因表达谱分析，上述核心外植体分别被无细胞水凝胶、加载外源性祖细胞的水凝胶，或加载外源性巨噬细胞的水凝胶所包裹；2）针对包裹于野生型或敲除型肌腱核心外植体周围的外源性祖细胞的RNA测序（RNA-seq）数据开展比较基因表达谱分析。