破骨细胞分化中甲基化改变基因的鉴定及其在骨质疏松症中的作用。

IF 2.6 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

DNA and cell biology Pub Date : 2022-06-01 DOI:10.1089/dna.2021.0699

Renpeng Peng, Yimin Dong, Honglei Kang, Qian Guo, Meipeng Zhu, Feng Li

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引用次数: 4

摘要

骨质疏松症是最常见的代谢性骨骼疾病之一，影响着全球2亿多人，尤其是老年人和绝经后妇女。骨质疏松症的主要过程之一是骨形成减弱。大量证据证实，过度活化的破骨细胞是骨形成减弱的原因。本研究旨在通过综合分析甲基化谱和基因表达数据，确定破骨细胞中新的甲基化相关生物标志物和治疗靶点。DNA甲基化图谱和基因表达数据来自基因表达综合数据库（GEO）。随后，我们整合了两组数据，以筛选来自供体的破骨细胞和CD14+单核细胞之间具有差异甲基化水平（DM-DEG）的差异表达基因。然后，进行基因本体论（GO）分析和京都基因和基因组百科全书（KEGG）通路分析，以揭示已鉴定的DM DEG的丰富功能和通路。此外，通过结合蛋白质-蛋白质相互作用分析和受体操作员特征分析，我们最终确定了四个中枢DM DEG。利用基因集富集分析来验证和研究四个中枢DM DEG的潜在生物学功能。最后，进行实时定量PCR（QPCR）以验证破骨细胞分化过程中四种已鉴定的中枢DM DEG的mRNA表达水平。CCRL2、CCL18、C1QB和SELL与破骨细胞分化和骨质疏松表型高度相关。QPCR显示，在破骨细胞分化过程中，CCRL2、CCL18和C1QB的表达增加，而SELL的表达减少。本研究表明，在破骨细胞分化过程中，基因表达和DNA甲基化之间存在联系，破骨细胞生成和骨质疏松症发病机制中的四个中枢DM-DEG可能是深入研究和治疗骨质疏松症的潜在候选靶点。

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Identification of Genes with Altered Methylation in Osteoclast Differentiation and Its Roles in Osteoporosis.

Osteoporosis is one of the most common metabolic skeletal diseases, which affects more than 200 million people worldwide, especially elderly and postmenopausal women. One of the main processes of osteoporosis is attenuated bone formation. Abundant evidence has confirmed that overactivated osteoclasts are responsible for the attenuated bone formation. This study aims at identifying novel methylation-associated biomarkers and therapeutic targets in osteoclasts by integrally analyzing methylation profiles and gene expression data. DNA methylation profile and gene expression data were obtained from the Gene Expression Omnibus (GEO) database. Subsequently, we integrated the two sets of data to screen for differentially expressed genes with differential methylation level (DM-DEGs) between osteoclasts and CD14+ monocytes from donors. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to uncover the enriched functions and pathways of identified DM-DEGs. In addition, by combining protein-protein interaction analysis and receiver-operator characteristic analysis, we finally identified four hub DM-DEGs. Gene Set Enrichment Analysis was utilized to validate and investigate the potential biological functions of the four hub DM-DEGs. Finally, Real-time quantitative PCR (QPCR) was performed to validate the mRNA expression level of the four identified hub DM-DEGs during osteoclast differentiation. CCRL2, CCL18, C1QB, and SELL were highly correlated with osteoclastic differentiation and osteoporosis phenotype. QPCR revealed that the expression of CCRL2, CCL18, and C1QB was increased during osteoclast differentiation, whereas the expression of SELL was decreased. The present study indicated a connection between gene expression and DNA methylation during osteoclast differentiation and that four hub DM-DEGs in osteoclastogenesis and osteoporosis pathogenesis might be potential candidates for intensive research and therapeutic targets for the treatment of osteoporosis.

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来源期刊

DNA and cell biology 生物-生化与分子生物学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

1.5 months

期刊介绍： DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward. DNA and Cell Biology coverage includes: Gene Structure, Function, and Regulation Gene regulation Molecular mechanisms of cell activation Mechanisms of transcriptional, translational, or epigenetic control of gene expression Molecular Medicine Molecular pathogenesis Genetic approaches to cancer and autoimmune diseases Translational studies in cell and molecular biology Cellular Organelles Autophagy Apoptosis P bodies Peroxisosomes Protein Biosynthesis and Degradation Regulation of protein synthesis Post-translational modifications Control of degradation Cell-Autonomous Inflammation and Host Cell Response to Infection Responses to cytokines and other physiological mediators Evasive pathways of pathogens.