CircRNA_28313/miR-195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice
CircRNA_28313/miR-195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice
复制标题
CircRNA_28313/miR-195a/CSF1轴调节破骨细胞分化影响OVX诱导的小鼠骨吸收
DOI：
10.1080/15476286.2019.1624470
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发表时间：
2019-06-20
期刊：
影响因子：
4.1
通讯作者：
Peng, Dan
中科院分区：
文献类型：
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作者：
Chen, Xia;Ouyang, Zhengxiao;Peng, Dan
成骨细胞骨形成和破骨细胞骨吸收动态维持骨稳态；在本研究中，我们试图从非编码RNA调控的角度探讨破骨细胞过度激活诱导骨稳态失调的机制。在未处理和RANKL + csf1处理的骨髓单核/巨噬细胞（BMM）细胞中检测了circrna的差异表达模式，并分析和鉴定了破骨细胞分化过程中差异表达的mirna。我们发现circRNA_28313被RANKL + CSF1显著诱导。circRNA_28313敲低在体外显著抑制RANKL + csf1诱导的BMM细胞内破骨细胞的分化，在体内抑制OVX诱导的小鼠骨吸收。通过生物信息学分析，已经证明miR-195a可能与circRNA_28313和CSF1结合，并共同形成circRNA-miRNA-mRNA网络。circRNA_28313通过作为ceRNA来缓解mir -195a介导的对CSF1的抑制，从而调节BMM细胞中的破骨细胞分化。综上所述，circRNA_28313、miR-195a和CSF1形成一个ceRNA网络，在RANKL + CSF1诱导的破骨细胞分化中发挥作用，从而影响ovx诱导的小鼠骨吸收。
ABSTRACT Osteoblastic bone formation and osteoclastic bone resorption dynamically maintain the bone homeostasis; in the present study, we attempt to investigate the mechanism of the excessive activation of osteoclasts inducing the deregulation of bone homeostasis from the perspective of non-coding RNA regulation. Differentially expressed patterns of circRNAs were examined in non-treated and RANKL + CSF1-treated bone marrow monocyte/macrophage (BMM) cells and differentially-expressed miRNAs during osteoclast differentiation were analyzed and identified. We found that circRNA_28313 was significantly induced by RANKL + CSF1 treatment. circRNA_28313 knockdown significantly inhibited RANKL + CSF1-induced differentiation of osteoclasts within BMM cells in vitro, while suppressed ovariectomized (OVX)-induced bone resorption in mice in vivo. Via bioinformatics analyses, it has been demonstrated that miR-195a might bind to circRNA_28313 and CSF1 and together form a circRNA-miRNA-mRNA network. circRNA_28313 relieves miR-195a-mediated suppression on CSF1 via acting as a ceRNA, therefore modulating the osteoclast differentiation in BMM cells. In conclusion, circRNA_28313, miR-195a, and CSF1 form a ceRNA network to function in RANKL + CSF1-induced osteoclast differentiation, thus affecting OVX-induced bone absorption in mice.