首页|慢性骨髓炎患者骨组织的转录组特征分析

慢性骨髓炎患者骨组织的转录组特征分析

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  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
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。
Transcriptomic characteristics analysis of bone from chronic osteomyelitis
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 im-munohistochemical analysis.Results A total of 5548 differentially expressed genes were obtained by high throughput sequenc-ing 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 ki-nase 7,MAP3K7),(nuclear factor of activated t cells 1,NFATC1)and(nuclear factor Kappa B subunit 2,NFκB2).In rat os-teomyelitis 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 os-teomyelitis,and the key genes IκBKβ,MAP3K7,NFATC1,NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

TranscriptomicsChronic osteomyelitisMAPK pathwayOsteoclast differentiation pathway

张扬、刘亦杨、沈立锋、林炳远、寿旦、郭峭峰、张春

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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

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

浙江大学医学院附属邵逸夫医院骨科,浙江杭州 310005

浙江中医药大学药学院,浙江 杭州 310053

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转录组学 慢性骨髓炎 MAPK信号通路 破骨细胞分化信号通路

浙江省基础公益研究计划浙江省基础公益研究计划浙江省基础公益研究计划浙江省基础公益研究计划浙江省中医药科技计划浙江省中医药科技计划

LGF19H060007LGF20H060004LGF21H280004LY20H2700022021ZA0332021ZB060

2024

10.12200/j.issn.1003-0034.20221149

中国骨伤
中国中西医结合学会,中国中医研究院

中国骨伤

CSTPCD
影响因子：1.876
ISSN：1003-0034
年,卷(期)：2024.37(5)
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