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人体全关节置换术后的无菌性松动由 miR-1246 和 miR-6089 通过 Wnt 信号通路调控。

Aseptic loosening around total joint replacement in humans is regulated by miR-1246 and miR-6089 via the Wnt signalling pathway.

机构信息

Australian National University Medical School, Canberra, Australia.

Department of Orthopaedic Surgery, Canberra Hospital, Canberra, Australia.

出版信息

J Orthop Surg Res. 2024 Jan 29;19(1):94. doi: 10.1186/s13018-024-04578-2.

DOI:10.1186/s13018-024-04578-2
PMID:38287447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10823634/
Abstract

BACKGROUND

Total joint replacement for osteoarthritis is one of the most successful surgical procedures in modern medicine. However, aseptic loosening continues to be a leading cause of revision arthroplasty. The diagnosis of aseptic loosening remains a challenge as patients are often asymptomatic until the late stages. MicroRNA (miRNA) has been demonstrated to be a useful diagnostic tool and has been successfully used in the diagnosis of other diseases. We aimed to identify differentially expressed miRNA in the plasma of patients with aseptic loosening.

METHODS

Adult patients undergoing revision arthroplasty for aseptic loosening and age- and gender-matched controls were recruited. Samples of bone, tissue and blood were collected, and RNA sequencing was performed in 24 patients with aseptic loosening and 26 controls. Differentially expressed miRNA in plasma was matched to differentially expressed mRNA in periprosthetic bone and tissue. Western blot was used to validate protein expression.

RESULTS

Seven miRNA was differentially expressed in the plasma of patients with osteolysis (logFC >|2|, adj-P < 0.05). Three thousand six hundred and eighty mRNA genes in bone and 427 mRNA genes in tissue samples of osteolysis patients were differentially expressed (logFC >|2|, adj-P < 0.05). Gene enrichment analysis and pathway analysis revealed two miRNA (miR-1246 and miR-6089) had multiple gene targets in the Wnt signalling pathway in the local bone and tissues which regulate bone metabolism.

CONCLUSION

These results suggest that aseptic loosening may be regulated by miR-1246 and miR-6089 via the Wnt signalling pathway.

摘要

背景

全关节置换术是现代医学中最成功的手术之一。然而，无菌性松动仍然是翻修关节置换术的主要原因。无菌性松动的诊断仍然是一个挑战，因为患者通常在晚期才出现无症状。MicroRNA（miRNA）已被证明是一种有用的诊断工具，并已成功应用于其他疾病的诊断。我们旨在确定无菌性松动患者血浆中差异表达的 miRNA。

方法

招募了因无菌性松动而行翻修关节置换术的成年患者和年龄、性别匹配的对照组。采集骨、组织和血液样本，并对 24 例无菌性松动患者和 26 例对照组进行 RNA 测序。将血浆中差异表达的 miRNA 与假体周围骨和组织中的差异表达的 mRNA 相匹配。使用 Western blot 验证蛋白质表达。

结果

在骨溶解患者的血浆中有 7 种 miRNA 差异表达（logFC> |2|，adj-P\ < 0.05）。骨溶解患者的骨和组织样本中有 3680 个 mRNA 基因和 427 个 mRNA 基因差异表达（logFC> |2|，adj-P\ < 0.05）。基因富集分析和通路分析显示，局部骨和组织中的 Wnt 信号通路中有两个 miRNA（miR-1246 和 miR-6089）有多个基因靶点，调节骨代谢。

结论

这些结果表明，无菌性松动可能通过 Wnt 信号通路被 miR-1246 和 miR-6089 调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/4884fd264fbd/13018_2024_4578_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/5e622e7eab88/13018_2024_4578_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/c51113a7b593/13018_2024_4578_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/cebfeb7c191d/13018_2024_4578_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/9001bd345000/13018_2024_4578_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/62d8fe2462f6/13018_2024_4578_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/35a8e02e0b1e/13018_2024_4578_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/4884fd264fbd/13018_2024_4578_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/5e622e7eab88/13018_2024_4578_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/c51113a7b593/13018_2024_4578_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/cebfeb7c191d/13018_2024_4578_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/9001bd345000/13018_2024_4578_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/62d8fe2462f6/13018_2024_4578_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/35a8e02e0b1e/13018_2024_4578_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a491/10823634/4884fd264fbd/13018_2024_4578_Fig7_HTML.jpg

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