鉴定与地方性关节炎--卡辛-贝克病中硫酸软骨素治疗反应相关的细胞特异性表观遗传模式。

IF 4.7 2区医学 Q2 CELL & TISSUE ENGINEERING

Bone & Joint Research Pub Date : 2024-05-17 DOI:10.1302/2046-3758.135.BJR-2023-0271.R1

Bolun Cheng, Cuiyan Wu, Wenming Wei, Hui Niu, Yan Wen, Cheng Li, Ping Chen, Hong Chang, Zhengjun Yang, Feng Zhang

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引用次数: 0

摘要

目的：在开始硫酸软骨素治疗前，使用从卡辛-贝克病（KBD）患者采集的外周血，评估与硫酸软骨素反应相关的细胞特异性 DNA 甲基化的改变：方法：在硫酸软骨素治疗的基线期采集 KBD 患者的外周血样本。使用还原表示亚硫酸氢盐测序（RRBS）生成外周血甲基化图谱。使用 MethylKit 鉴定了差异甲基化区域（DMR），DMR 相关基因被定义为注释到 DMR 的基因体或 2.2 千碱基上游区域的基因。通过定量反转录聚合酶链反应（qRT-PCR）评估表达水平，进一步验证了选定的 DMR 相关基因。通过张量成分分析，从大块组织中确定细胞特异性DNA甲基化差异：结果：这项研究发现了21,060个高甲基化和44,472个低甲基化的DMRs，以及13,194个高甲基化和22,448个低甲基化的CpG岛，这些都是硫酸软骨素治疗反应的全局甲基化差异。共有 12,666 个 DMR 相关基因的启动子区域含有 DMR，如 CHL1（错误发现率 (FDR) = 2.11 × 10-11）、RIC8A（FDR = 7.05 × 10-4）和 SOX12（FDR = 1.43 × 10-3）。此外，RIC8A 和 CHL1 在应答者中呈高甲基化，而 SOX12 在应答者中呈低甲基化，均显示基因表达下降。我们观察了与硫酸软骨素反应相关的细胞特异性全局甲基化差异模式。具体来说，我们发现在粒细胞、单核细胞和 B 细胞中，位于 TESPA1 和 ATP11A 的 DMRs 在应答者和非应答者之间表现出不同的 DNA 甲基化：我们的研究发现了与 KBD 患者硫酸软骨素反应相关的 DNA 甲基化特异性细胞变化。

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Identification of cell-specific epigenetic patterns associated with chondroitin sulfate treatment response in an endemic arthritis, Kashin-Beck disease.

Aims: To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Methods: Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.

Results: This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10^-11), RIC8A (FDR = 7.05 × 10^-4), and SOX12 (FDR = 1.43 × 10^-3). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells.