创伤后肘关节僵硬发病机制的新临床见解：人类挛缩关节囊的表达谱分析

Novel Clinical Insights into the Pathogenesis of Posttraumatic Elbow Stiffness: An Expression Profile Analysis of Contracted Joint Capsule in Human.

作者信息

Liu Nan, Dong Jinlei, Li Lianxin, Xu Jiajun, Yang Changhao, Yu Zhanchuan, Liu Fanxiao

机构信息

Department of Shandong Trauma Center, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250014, People's Republic of China.

Department of Shandong Trauma Center, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250014, People's Republic of China.

出版信息

J Inflamm Res. 2025 Jan 6;18:167-182. doi: 10.2147/JIR.S499986. eCollection 2025.

DOI:10.2147/JIR.S499986

PMID:39802512

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11721169/

Abstract

BACKGROUND

Posttraumatic elbow stiffness is a complex complication with two characteristics of capsular contracture and heterotopic ossification. Currently, genomic mechanisms and pathogenesis of posttraumatic elbow stiffness remain inadequately understood. This study aims to identify differentially expressed genes (DEGs) and elucidate molecular networks of posttraumatic elbow stiffness, providing novel insights into disease mechanisms at transcriptome level.

METHODS

Global transcriptome sequencing was conducted on six capsular samples from individuals with posttraumatic elbow stiffness and three control capsular samples from individuals with elbow fractures. Differentially expressed genes (DEGs), microRNAs, and long non-coding RNAs (LncRNAs) were identified and analyzed. Functional enrichment analysis was performed, and the associated protein-protein interaction (PPI) network was constructed. MicroRNAs targeting these DEGs were identified, and transcription factors (TFs) targeting DEGs were predicted using the ENCODE database. Finally, key DEGs were validated by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

A total of 4909 DEGs associated with protein-coding, LncRNA and microRNA were detected, including 2124 upregulated and 2785 downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were significantly enriched in 36 signaling pathways, notably involving inflammatory responses and extracellular matrix (ECM) receptor interactions. The protein-protein interaction (PPI) network analysis highlighted genes such as SPP1, IBSP, MMP13 and MYO1A as having higher degrees of connectivity. Key microRNAs (hsa-miR-186-5p, hsa-miR-515-5p, and hsa-miR-590-3p) and transcription factors (TFDP1 and STAT3) were predicted to be implicated in the pathogenesis of posttraumatic elbow stiffness through the microRNA-transcription factor regulatory network analysis.

CONCLUSION

The study provided insights into the molecular mechanisms underlying the changes in the contracted capsules associated with posttraumatic elbow stiffness. Hub genes including SPP1, IBSP, MMP13, and MYO1A, key microRNAs (has-miR-186-5p, has-miR-515-5p, hsa-miR-590-3p) and TFs (TFDP1 and STAT3) may serve as prognostic and therapeutic targets of posttraumatic elbow stiffness, and provide a new idea for the future research direction of clinical treatment.

摘要

背景

创伤后肘关节僵硬是一种复杂的并发症，具有关节囊挛缩和异位骨化两个特征。目前，创伤后肘关节僵硬的基因组机制和发病机制仍未得到充分了解。本研究旨在鉴定差异表达基因（DEGs）并阐明创伤后肘关节僵硬的分子网络，在转录组水平上为疾病机制提供新的见解。

方法

对6例创伤后肘关节僵硬患者的关节囊样本和3例肘关节骨折患者的对照关节囊样本进行全转录组测序。鉴定并分析差异表达基因（DEGs）、微小RNA和长链非编码RNA（LncRNAs）。进行功能富集分析，并构建相关的蛋白质-蛋白质相互作用（PPI）网络。鉴定靶向这些DEGs的微小RNA，并使用ENCODE数据库预测靶向DEGs的转录因子（TFs）。最后，通过定量实时聚合酶链反应（qRT-PCR）验证关键DEGs。

结果

共检测到4909个与蛋白质编码、LncRNA和微小RNA相关的DEGs，其中上调2124个，下调2785个。京都基因与基因组百科全书（KEGG）通路分析显示，这些DEGs在36条信号通路中显著富集，尤其涉及炎症反应和细胞外基质（ECM）受体相互作用。蛋白质-蛋白质相互作用（PPI）网络分析突出了如SPP1、IBSP、MMP13和MYO1A等具有较高连接度的基因。通过微小RNA-转录因子调控网络分析，预测关键微小RNA（hsa-miR-186-5p、hsa-miR-515-5p和hsa-miR-590-3p）和转录因子（TFDP1和STAT3）与创伤后肘关节僵硬的发病机制有关。

结论

本研究为创伤后肘关节僵硬相关挛缩关节囊变化的分子机制提供了见解。包括SPP1、IBSP、MMP13和MYO1A在内的枢纽基因、关键微小RNA（has-miR-186-5p、has-miR-515-5p、hsa-miR-590-3p）和转录因子（TFDP1和STAT3）可能作为创伤后肘关节僵硬的预后和治疗靶点，并为临床治疗的未来研究方向提供新思路。