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血清 snoRNA 作为关节老化和创伤后骨关节炎的生物标志物。

Serum snoRNAs as biomarkers for joint ageing and post traumatic osteoarthritis.

机构信息

Department of Orthopedic Surgery, Caphri School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, the Netherlands.

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

出版信息

Sci Rep. 2017 Mar 2;7:43558. doi: 10.1038/srep43558.

Abstract

The development of effective treatments for the age-related disease osteoarthritis and the ability to predict disease progression has been hampered by the lack of biomarkers able to demonstrate the course of the disease. Profiling the expression patterns of small nucleolar RNAs (snoRNAs) in joint ageing and OA may provide diagnostic biomarkers and therapeutic targets. This study determined expression patterns of snoRNAs in joint ageing and OA and examined them as potential biomarkers. Using SnoRNASeq and real-time quantitative PCR (qRT-PCR) we demonstrate snoRNA expression levels in murine ageing and OA joints and serum for the first time. SnoRNASeq identified differential expression (DE) of 6 snoRNAs in young versus old joints and 5 snoRNAs in old sham versus old experimental osteoarthritic joints. In serum we found differential presence of 27 snoRNAs in young versus old serum and 18 snoRNAs in old sham versus old experimental osteoarthritic serum. Confirmatory qRT-PCR analysis demonstrated good correlation with SnoRNASeq findings. Profiling the expression patterns of snoRNAs is the initial step in determining their functional significance in ageing and osteoarthritis, and provides potential diagnostic biomarkers and therapeutic targets. Our results establish snoRNAs as novel markers of musculoskeletal ageing and osteoarthritis.

摘要

有效治疗与年龄相关的骨关节炎疾病以及预测疾病进展的能力一直受到缺乏能够证明疾病进程的生物标志物的阻碍。对小核仁 RNA(snoRNA)在关节老化和 OA 中的表达模式进行分析,可能为诊断生物标志物和治疗靶点提供依据。本研究首次确定了关节老化和 OA 中 snoRNA 的表达模式,并将其作为潜在的生物标志物进行了研究。通过 snoRNA-seq 和实时定量 PCR(qRT-PCR),我们首次在鼠类老化和 OA 关节及血清中证明了 snoRNA 的表达水平。snoRNA-seq 鉴定了年轻关节与老年关节、老年 sham 关节与老年实验性骨关节炎关节之间的 6 个 snoRNA 和 5 个 snoRNA 的差异表达。在血清中,我们发现年轻血清与老年血清之间存在 27 个 snoRNA 的差异表达,老年 sham 关节与老年实验性骨关节炎关节之间存在 18 个 snoRNA 的差异表达。qRT-PCR 分析验证了与 snoRNA-seq 结果的良好相关性。对 snoRNA 表达模式的分析是确定其在老化和骨关节炎中功能意义的初始步骤,并为诊断生物标志物和治疗靶点提供了依据。我们的研究结果确立 snoRNA 为肌肉骨骼老化和骨关节炎的新型标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e97/5333149/3a25418eebff/srep43558-f1.jpg

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