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微小RNA-150-5p通过靶向维生素D受体抑制强直性脊柱炎中成纤维细胞的成骨分化。

miR-150-5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR.

作者信息

Li Yuan, Qi Wufang, Shi Yuquan

机构信息

Department of Rheumatology and Immunology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.

出版信息

Exp Ther Med. 2022 Apr;23(4):283. doi: 10.3892/etm.2022.11213. Epub 2022 Feb 15.

Abstract

Dysregulated microRNAs (miRNAs or miRs) serve potential roles in inflammatory systemic disease, including ankylosing spondylitis (AS). The aim of the present study was to investigate the potential function of miR-150-5p in osteogenic differentiation of AS fibroblasts and its underlying mechanism. The expression of miR-150-5p and vitamin D receptor (VDR) in AS joint capsules and fibroblasts was detected by reverse transcription-quantitative (RT-q)PCR and western blotting. Following overexpression of miR-150-5p, the alteration in osteogenic gene expression was detected by RT-qPCR, western blotting and alkaline phosphatase activity assay, as well as alizarin red staining. The association between miR-150-5p and VDR was confirmed by luciferase assay and rescue experiments were performed. Patients with AS exhibited decreased expression of miR-150-5p in joint capsules. Treatment with bone morphogenic protein 2 (BMP-2) and transforming growth factor-β1 (TGF-β1) led to downregulation of miR-150-5p in AS fibroblasts. Enforced expression of miR-150-5p attenuated osteogenic differentiation of AS fibroblasts. These results demonstrated that miR-150-5p inhibited osteogenic differentiation of AS fibroblasts by targeting VDR. miR-150-5p overexpression decreased osteogenic transformation of fibroblasts by decreasing VDR expression in AS.

摘要

失调的微小RNA(miRNA或miR)在包括强直性脊柱炎(AS)在内的炎症性全身性疾病中发挥潜在作用。本研究的目的是探讨miR-150-5p在AS成纤维细胞成骨分化中的潜在功能及其潜在机制。通过逆转录定量(RT-q)PCR和蛋白质印迹法检测AS关节囊和成纤维细胞中miR-150-5p和维生素D受体(VDR)的表达。在miR-150-5p过表达后,通过RT-qPCR、蛋白质印迹法、碱性磷酸酶活性测定以及茜素红染色检测成骨基因表达的变化。通过荧光素酶测定证实了miR-150-5p与VDR之间的关联,并进行了挽救实验。AS患者关节囊中miR-150-5p表达降低。用骨形态发生蛋白2(BMP-2)和转化生长因子-β1(TGF-β1)处理导致AS成纤维细胞中miR-150-5p下调。miR-150-5p的强制表达减弱了AS成纤维细胞的成骨分化。这些结果表明,miR-150-5p通过靶向VDR抑制AS成纤维细胞的成骨分化。miR-150-5p过表达通过降低AS中VDR的表达减少了成纤维细胞的成骨转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b78b/8908459/4b2b685bd823/etm-23-04-11213-g00.jpg

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