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泼尼松龙通过斑马鱼幼体中的粘着斑信号通路诱导骨质疏松样表型。

Prednisolone induces osteoporosis-like phenotypes via focal adhesion signaling pathway in zebrafish larvae.

作者信息

Huo Lei, Wang Lei, Yang Zhaoyao, Li Pingyuan, Geng Dechun, Xu Yaozeng

机构信息

Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, Shi Zi Road, Suzhou 215006, China.

Department of Orthopedics, Suzhou Science & Technology Town Hospital, 1 Lijiang Road, New District, Suzhou 215010, China.

出版信息

Biol Open. 2018 Jul 16;7(7):bio029405. doi: 10.1242/bio.029405.

Abstract

Patients taking glucocorticoid or glucocorticoid-like drugs for an extended period of time may develop osteoporosis, termed glucocorticoid-induced osteoporosis (GIOP). GIOP is the most common form of secondary osteoporosis, but the mechanism underlying its development is unclear. In the present study, we used prednisolone to treat zebrafish larvae to investigate GIOP. Our RNA deep-sequencing (RNA-seq) results show that prednisolone affects genes known to act in the extracellular region. Therefore the extracellular region, extracellular matrix, and collagen trimer might be involved in glucocorticoid-induced osteoporosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the focal adhesion signaling pathway is the most enriched signaling pathway in terms of differentially expressed genes (DEGs). In this pathway, () and (), genes encoding two adapter proteins, were down-regulated in the prednisolone-treated larvae. Further experiments showed that prednisolone contributes to GIOP by down-regulating and .

摘要

长期服用糖皮质激素或糖皮质激素样药物的患者可能会发生骨质疏松,称为糖皮质激素诱导的骨质疏松症(GIOP)。GIOP是继发性骨质疏松症最常见的形式,但其发病机制尚不清楚。在本研究中,我们使用泼尼松龙处理斑马鱼幼体以研究GIOP。我们的RNA深度测序(RNA-seq)结果表明,泼尼松龙影响已知在细胞外区域起作用的基因。因此,细胞外区域、细胞外基质和胶原三聚体可能参与糖皮质激素诱导的骨质疏松症。京都基因与基因组百科全书(KEGG)通路分析显示,就差异表达基因(DEG)而言,粘着斑信号通路是最富集的信号通路。在该通路中,编码两种衔接蛋白的基因()和()在泼尼松龙处理的幼体中下调。进一步的实验表明,泼尼松龙通过下调和导致GIOP。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a35a/6078353/bd7da7e14925/biolopen-7-029405-g1.jpg

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