Irisin directly stimulates osteoclastogenesis and bone resorption in vitro and in vivo: RNAseq dataset

Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts and osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. In vitro, irisin (2–10 ng/mL) increased osteoclast differentiation in C57BL/6J mouse bone marrow progenitors; however, this increase was blocked by a neutralizing antibody to integrin αVβ5. Irisin also increased bone resorption on several substrates in situ. RNAseq revealed differential gene expression induced by irisin including upregulation of markers for osteoclast differentiation and resorption, as well as osteoblast-stimulating ‘clastokines’. Forced expression of the irisin precursor Fndc5 in transgenic C57BL/6J mice resulted in lower bone mass at three ages and greater in vitro osteoclastogenesis from Fndc5-transgenic bone marrow progenitors. This study demonstrates that irisin acts directly on osteoclast progenitors to increase differentiation and pro...鸢尾素（Irisin）是一种由骨骼肌分泌的肌因子（myokine），可通过作用于成骨细胞（osteoblasts）与骨细胞（osteocytes），在一定程度上促进骨肌串扰与骨骼重塑。本研究旨在探究鸢尾素是否可直接调控破骨细胞（osteoclasts）。体外实验显示，浓度为2~10 ng/mL的鸢尾素可促进C57BL/6J小鼠骨髓祖细胞的破骨细胞分化；但该促分化效应可被整合素αVβ5的中和性抗体阻断。鸢尾素还可在原位状态下于多种底物上增强骨吸收活性。转录组测序（RNAseq）结果显示，鸢尾素可诱导差异基因表达，其中包括破骨细胞分化与骨吸收相关标志物的上调，以及可刺激成骨细胞的"破细胞因子（clastokines）"。在转基因C57BL/6J小鼠中强制表达鸢尾素前体Fndc5后，小鼠在三个年龄阶段的骨量均更低，且其骨髓祖细胞的体外破骨细胞生成能力更强。本研究证实，鸢尾素可直接作用于破骨细胞祖细胞，以增强其分化及……