慢性骨髓炎患者骨组织的转录组特征分析
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作者Author单位AddressE-Mail
张扬 ZHANG Yang 浙江中医药大学附属第一医院 浙江省中医院骨伤研究所, 浙江 杭州 310053 Institute of Orthopaedics and Traumatology, the First Affliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, Zhejiang, China  
刘亦杨 LIU Yi-yang 南京中医药大学中西医结合临床医学院 南京鼓楼医院, 江苏 南京 210008
浙江省立同德医院骨伤科, 浙江 杭州 310012
Clinical Medical College of Integrated Traditional Chinese and Western Medicine of Nanjing University of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu, China
Department of Orthopaedics, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China
orthopaedic_liuyy@163.com 
沈立锋 SHEN Li-feng 浙江大学医学院附属邵逸夫医院骨科, 浙江 杭州 310005 Department of Orthopaedics, Sir Run Run Shaw Hospital affiliated with the Zhejiang University School of Medicine, Hangzhou 310005, Zhejiang, China  
林炳远 LIN Bing-yuan 浙江省立同德医院骨伤科, 浙江 杭州 310012 Department of Orthopaedics, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China  
寿旦 SHOU Dan 浙江中医药大学药学院, 浙江 杭州 310053 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China  
郭峭峰 GUO Qiao-feng 浙江省立同德医院骨伤科, 浙江 杭州 310012 Department of Orthopaedics, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China  
张春 ZHANG Chun 浙江省立同德医院骨伤科, 浙江 杭州 310012 Department of Orthopaedics, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China  
期刊信息:《中国骨伤》2024年,第37卷,第5期,第519-526页
DOI:10.12200/j.issn.1003-0034.20221149
基金项目:浙江省基础公益研究计划(编号:LGF19H060007,LGF20H060004;LGF21H280004;LY20H270002);浙江省中医药科技计划(编号:2021ZA033,2021ZB060)
中文摘要:

目的:采集和分析慢性骨髓炎患者骨组织的转录组信息,为探究慢性骨髓炎发病的分子机制,明确MAPK信号通路在慢性骨髓炎发病过程中的作用。

方法:收集2019年6月至2020年6月就诊的四肢创伤性骨髓炎4例,病灶骨样本(Necrosis组)以及正常骨组织(Control组),使用Illumina HiSeq Xten高通量测序平台采集转录组信息,并采用FPKM方法计算基因在骨组织中的表达量。通过对比病灶组织与正常组织的转录本水平,筛选差异基因,并进行GO富集和KEGG富集。采用大鼠骨髓炎动物模型,选取细胞外信号调节酶MAP3K7(mitogen-activated protein 3 kinase 7)、活化T细胞核因子1(nuclear factor of activated T cells 1,NFATC1)做差异靶点的免疫组化学的验证。

结果:高通量测序共获得5 548个差异基因,其中Necrosis组上调 2 701个,下调2 847个。筛选正常骨组织和病灶骨的差异基因中富集到MAPK信号通路的基因,并与破骨细胞分化(osteoclast differentiation)信号通路相关的基因取交集,共有基因为核因子κB激酶亚基β抑制剂IκBKβ(inhibitor of nuclear factor kappa B kinase subunit beta)、MAP3K7、NFATC1、核因子κB亚基2(nuclear factor kappa B subunit 2,NFκB2)。在大鼠骨髓炎模型中,MAP3K7、NFATC1在骨髓以及损伤骨组织周围高表达。

结论:基于转录组学分析显示慢性骨髓炎的发病和MAPK信号通路相关,IκBKβ、MAP3K7、NFATC1、NFκB2有可能成为新的临床诊断和疾病治疗的靶点。
【关键词】转录组学  慢性骨髓炎  MAPK信号通路  破骨细胞分化信号通路
 
Transcriptomic characteristics analysis of bone from chronic osteomyelitis
ABSTRACT  

Objective To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis,by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis.

Methods Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected,and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group),and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform,and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments,by using rat osteomyelitis animal model and immunohistochemical analysis.

Results A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group,including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened,the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta,IκBKβ),(mitogen-activated protein kinase 7,MAP3K7),(nuclear factor of activated t cells 1,NFATC1) and (nuclear factor Kappa B subunit 2,NFκB2). In rat osteomyelitis model,MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue.

Conclusion Based on the transcriptome analysis,the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis,and the key genes IκBKβ,MAP3K7,NFATC1,NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.
KEY WORDS  Transcriptomics  Chronic osteomyelitis  MAPK pathway  Osteoclast differentiation pathway
 
引用本文,请按以下格式著录参考文献:
中文格式:张扬,刘亦杨,沈立锋,林炳远,寿旦,郭峭峰,张春.慢性骨髓炎患者骨组织的转录组特征分析[J].中国骨伤,2024,37(5):519~526
英文格式:ZHANG Yang,LIU Yi-yang,SHEN Li-feng,LIN Bing-yuan,SHOU Dan,GUO Qiao-feng,ZHANG Chun.Transcriptomic characteristics analysis of bone from chronic osteomyelitis[J].zhongguo gu shang / China J Orthop Trauma ,2024,37(5):519~526
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