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miR-181a-5p 通过靶向 BMP3 促进成骨。

MiR-181a-5p promotes osteogenesis by targeting BMP3.

机构信息

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, China.

出版信息

Aging (Albany NY). 2023 Feb 3;15(3):734-747. doi: 10.18632/aging.204505.

Abstract

High-throughput microRNA (miRNA) sequencing of osteoporosis was analyzed from the Gene Expression Omnibus (GEO) database to investigate specific microRNAs that control osteogenesis. MiR-181a-5p was differentially expressed among healthy subjects and those with osteoporosis. Inhibitors and mimics were transfected into cells to modulate miR-181a-5p levels to examine the role in MC3T3-E1 functions. Alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining were used for morphological detection, and proteins of ALP and Runt-related transcription factor 2 (RUNX2), as osteogenesis markers, were detected. During the osteogenic differentiation of MC3T3-E1, the transcription level of miR-181a-5p was significantly increased. The inhibition of miR-181a-5p suppressed MC3T3-E1 osteogenic differentiation, whereas its overexpression functioned oppositely. Consistently, the miR-181a-5p antagomir aggravated osteoporosis in old mice. Additionally, we predicted potential target genes via TargetScan and miRDB and identified bone morphogenetic protein 3 (BMP3) as the target gene. Moreover, the reduced expression of miR-181a-5p was validated in our hospitalized osteoporotic patients. These findings have substantial implications for the strategies targeting miR-181a-5p to prevent osteoporosis and potential related fractures.

摘要

从基因表达综合数据库(GEO)中分析了骨质疏松症的高通量 microRNA(miRNA)测序,以研究控制成骨的特定 microRNAs。miR-181a-5p 在健康受试者和骨质疏松症患者之间存在差异表达。转染抑制剂和模拟物来调节 miR-181a-5p 水平,以研究其对 MC3T3-E1 功能的作用。碱性磷酸酶(ALP)染色和茜素红 S(ARS)染色用于形态学检测,检测成骨标志物 ALP 和 Runt 相关转录因子 2(RUNX2)的蛋白。在 MC3T3-E1 的成骨分化过程中,miR-181a-5p 的转录水平显著增加。抑制 miR-181a-5p 抑制 MC3T3-E1 成骨分化,而其过表达则相反。一致地,miR-181a-5p 拮抗剂加重了老年小鼠的骨质疏松症。此外,我们通过 TargetScan 和 miRDB 预测了潜在的靶基因,并确定骨形态发生蛋白 3(BMP3)为靶基因。此外,我们在住院的骨质疏松症患者中验证了 miR-181a-5p 的表达降低。这些发现对于针对 miR-181a-5p 预防骨质疏松症和潜在相关骨折的策略具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd84/9970307/f766beb0ccdf/aging-15-204505-g001.jpg

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