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长链非编码 RNA MIAT 可作为脆性骨折的生物标志物，并促进骨折愈合。

Long non-coding RNA MIAT serves as a biomarker of fragility fracture and promotes fracture healing.

机构信息

Department of Orthopedics, Liaocheng People's Hospital, No. 67, West Dongchang Road, Liaocheng, 252000, China.

Department of Nephrology, Liaocheng People's Hospital, Liaocheng, 252000, China.

出版信息

J Orthop Surg Res. 2024 Jun 8;19(1):343. doi: 10.1186/s13018-024-04824-7.

DOI:10.1186/s13018-024-04824-7
PMID:38849896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11162066/
Abstract

BACKGROUND

Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated.

METHODS

90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis.

RESULTS

Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation.

CONCLUSIONS

LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.

摘要

背景

脆性骨折在老年人中很常见。成骨细胞分化对于骨愈合和再生至关重要。本研究检测了长链非编码 RNA MIAT 在骨折愈合过程中的表达模式，并探讨了其在成骨细胞分化中的作用。

方法

纳入 90 例单纯骨质疏松症女性和 90 例脆性骨折女性，另设 90 例年龄匹配的女性作为对照组。采用 RT-qPCR 检测 mRNA 水平，CCK-8 法检测细胞活力，ELISA 法检测成骨细胞标志物 ALP、OCN、Collagen I 和 RUNX2。通过生物信息学分析预测 MIAT 的下游靶向 miRNA 和基因，通过 GO 和 KEGG 分析注释其功能和通路。

结果

血清 MIAT 在具有高诊断效能的骨质疏松症女性中上调，在脆性骨折组中甚至更高，但在手术后呈时间依赖性下降。MIAT 敲低促进 MC3T3-E1 的成骨增殖和分化，但被 miR-181a-5p 抑制剂逆转。基于 miRDB、TargetScan 和 microT 数据集，共预测到 miR-181a-5p 的 137 个重叠靶基因，这些基因主要富集于调节干细胞多能性、细胞衰老和破骨细胞分化的信号通路相关术语。

结论

lncRNA MIAT 可作为骨质疏松症有前途的生物标志物，通过靶向 miR-181a-5p 促进成骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/e9a68dcfa055/13018_2024_4824_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/81cdfce9b286/13018_2024_4824_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/bc5621ea1eef/13018_2024_4824_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/241e6f311ee9/13018_2024_4824_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/8322e1fa2bc4/13018_2024_4824_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/e9a68dcfa055/13018_2024_4824_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/81cdfce9b286/13018_2024_4824_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/bc5621ea1eef/13018_2024_4824_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/241e6f311ee9/13018_2024_4824_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/8322e1fa2bc4/13018_2024_4824_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11162066/e9a68dcfa055/13018_2024_4824_Fig2_HTML.jpg

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