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小鼠关节衰老和创伤后骨关节炎中的微小RNA特征

Mouse microRNA signatures in joint ageing and post-traumatic osteoarthritis.

作者信息

Castanheira Catarina I G D, Anderson James R, Fang Yongxiang, Milner Peter I, Goljanek-Whysall Katarzyna, House Louise, Clegg Peter D, Peffers Mandy J

机构信息

Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L7 8TX, UK.

Centre for Genomic Research, Institute of Systems, Molecular and Integrative Biology, Biosciences Building, Crown Street, University of Liverpool, Liverpool, L69 7ZB, UK.

出版信息

Osteoarthr Cartil Open. 2021 Dec;3(4):100186. doi: 10.1016/j.ocarto.2021.100186.

Abstract

OBJECTIVE

This study investigated mice serum and joint microRNA expression profiles in ageing and osteoarthritis to elucidate the role of microRNAs in the development and progression of disease, and provide biomarkers for ageing and osteoarthritis.

DESIGN

Whole joints and serum samples were collected from C57BL6/J male mice and subjected to small RNA sequencing. Groups used included; surgically-induced post-traumatic osteoarthritis, (DMM; 24 months-old); sham surgery (24 months-old); old mice (18 months-old); and young mice (8 months-old). Differentially expressed microRNAs between the four groups were identified and validated using real-time quantitative PCR. MicroRNA differential expression data was used for target prediction and pathway analysis.

RESULTS

In joint tissues, miR-140-5p, miR-205-5p, miR-682, miR-208b-3p, miR-499-5p, miR-455-3p and miR-6238 were differentially expressed between young and old groups; miR-146a-5p, miR-3474, miR-615-3p and miR-151-5p were differentially expressed between DMM and Sham groups; and miR-652-3p, miR-23b-3p, miR-708-5p, miR-5099, miR-23a-3p, miR-214-3p, miR-6238 and miR-148-3p between the old and DMM groups. The number of differentially expressed microRNAs in serum was higher, some in common with joint tissues including miR-140-5p and miR-455-3p between young and old groups; and miR-23b-3p, miR-5099 and miR-6238 between old and DMM groups.We confirmed miR-140-5p, miR-499-5p and miR-455-3p expression to be decreased in old mouse joints compared to young, suggesting their potential use as biomarkers of joint ageing in mice.

CONCLUSIONS

MiR-140-5p, miR-499-5p and miR-455-3p could be used as joint ageing biomarkers in mice. Further research into these specific molecules in human tissues is now warranted to check their potential suitability as human biomarkers of ageing.

摘要

目的

本研究调查了衰老和骨关节炎小鼠血清及关节中的微小RNA表达谱,以阐明微小RNA在疾病发生和发展中的作用,并为衰老和骨关节炎提供生物标志物。

设计

从C57BL6/J雄性小鼠收集全关节和血清样本,进行小RNA测序。使用的组包括:手术诱导的创伤后骨关节炎(DMM;24月龄);假手术(24月龄);老年小鼠(18月龄);和年轻小鼠(8月龄)。使用实时定量PCR鉴定并验证四组之间差异表达的微小RNA。微小RNA差异表达数据用于靶标预测和通路分析。

结果

在关节组织中,miR-140-5p、miR-205-5p、miR-682、miR-208b-3p、miR-499-5p、miR-455-3p和miR-6238在年轻组和老年组之间差异表达;miR-146a-5p、miR-3474、miR-615-3p和miR-151-5p在DMM组和假手术组之间差异表达;miR-652-3p、miR-23b-3p、miR-708-5p、miR-5099、miR-23a-3p、miR-214-3p、miR-6238和miR-148-3p在老年组和DMM组之间差异表达。血清中差异表达的微小RNA数量更多,一些与关节组织中的相同,包括年轻组和老年组之间的miR-140-5p和miR-455-3p;老年组和DMM组之间的miR-23b-3p、miR-5099和miR-6238。我们证实,与年轻小鼠相比,老年小鼠关节中miR-140-5p、miR-499-5p和miR-455-3p的表达降低,表明它们可能用作小鼠关节衰老的生物标志物。

结论

MiR-140-5p、miR-499-5p和miR-455-3p可作为小鼠关节衰老的生物标志物。现在有必要对人体组织中的这些特定分子进行进一步研究,以检查它们作为人类衰老生物标志物的潜在适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdbb/9718179/e6da364f6c70/gr1.jpg

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