The Role and Mechanism of miRNA-1224 in the Polygonatum sibiricum Polysaccharide Regulation of Bone Marrow-Derived Macrophages to Osteoclast Differentiation

The Role and Mechanism of miRNA-1224 in the Polygonatum sibiricum Polysaccharide Regulation of Bone Marrow-Derived Macrophages to Osteoclast Differentiation
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DOI:
10.1089/rej.2018.2126
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发表时间:
2019-10-01
影响因子:
2.6
通讯作者:
Zeng, Gaofeng
Zeng, Gaofeng
中科院分区:
医学3区
文献类型:
--
作者:
Li, Bo;Wu, Pingping;Zeng, Gaofeng

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microRNAs(miRNAs)是一种内源性非编码小分子RNA,可调控细胞增殖、分化、脂肪代谢和激素分泌。研究表明,miRNAs调控与骨质疏松相关的过程,包括成骨细胞、破骨细胞和软骨细胞的分化,是某些骨代谢疾病的重要调控因子之一。本课题组前期研究发现,天然复方黄精多糖(Polygonatum sibiricum polysaccharide,PSP)可通过Wnt/beta-catenin信号通路促进成骨细胞的形成,阻断破骨细胞的生成。本研究旨在探讨PSP是否能够通过Hippo信号通路抑制破骨细胞相关基因的表达,并通过有效阻断miR-1224的表达来阻止这种抑制作用。这项研究表明,当PSP抑制破骨细胞生成时,有27个差异表达的miRNAs,其中最显着的是miR-1224。此外,研究表明PSP增加了miR-1224靶基因Limd 1的水平。总之,这些发现表明PSP通过基于miR-1224的Hippo信号通路抑制体外破骨细胞生成。这项研究可能有助于开发一种利用PSP增强骨骼健康和预防骨质疏松症的治疗方法。
MicroRNAs (miRNAs) are endogenous noncoding small molecule RNAs that regulate cell proliferation, differentiation, fat metabolism, and hormone secretion. Studies have shown that miRNAs regulate the processes related to osteoporosis, including the differentiation of osteoblasts, osteoclasts, and chondrocytes, and are one of the important regulatory factors of some bone metabolic diseases. In our previous study, it has been revealed that natural compound Polygonatum sibiricum polysaccharide (PSP) can promote osteoblast formation and block osteoclastogenesis through Wnt/beta-catenin signaling pathway. This study was designed to investigate whether PSP can inhibit expression of osteoclast-related genes by Hippo signaling pathway, which was prevented by effectively blocking the expression of miR-1224. This study showed that there were 27 differentially expressed miRNAs when PSP inhibits osteoclastogenesis, the most notable of which was miR-1224. Furthermore, the study showed that PSP increased the level of Limd1, which was the target gene of miR-1224. In conclusion, these findings demonstrate that PSP suppressed osteoclastogenesis in vitro through the Hippo signaling pathway based on miR-1224. This study may aid in the development of a therapeutic approach utilizing PSP for the enhancement of bone health and prevention of osteoporosis.