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Genome-wide DNA methylation analysis of articular chondrocytes identifies TRAF1, CTGF, and CX3CL1 genes as hypomethylated in osteoarthritis

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Abstract

The aim of this study is to identify osteoarthritis (OA)-associated differentially methylated genes in human articular chondrocytes from patients with OA. DNA methylation profiling of articular chondrocytes from OA patients, rheumatoid arthritis (RA) patients, and controls was performed, and candidate genes were chosen for validation of gene demethylation status. The mRNA expression levels of candidate genes in chondrocytes were detected by real-time quantitative PCR. Chondrocytes from OA and RA group were treated with 5-Aza-2-deoxycytidine (5-Aza), and then the mRNA expression levels were detected. Forty-five genes with significant methylation differences between OA and control group were identified. Tumor necrosis factor receptor-associated factor 1 (TRAF1), connective tissue growth factor (CTGF), and chemokine (C-X3-C motif) ligand 1(CX3CL1) genes were hypomethylated in chondrocytes of OA and RA patients, which verified by bisulfite sequencing analysis. The mRNA expression level of TRAF1 and CTGF was significantly increased in OA and RA group (p < 0.05), while the expression level of CX3CL1 was only increased in OA group (p < 0.05). For the chondrocytes from OA and RA treated with 5-Aza, the mRNA expression level of TRAF1 and CTGF was highly increased (p < 0.05). It is the first time to show that TRAF1, CTGF, and CX3CL1 genes were hypomethylated in OA chondrocytes and have a consistent correlation with mRNA expression, which suggests that epigenetic changes in the methylation status of TRAF1, CTGF, and CX3CL1 contribute to the pathology of OA.

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Acknowledgements

We thank all the study participants who made this study possible and all the staff in the in the orthopedics department of Beijing Hospital, People’s Hospital of Pecking University and Beijing Jishuitan Hospital operating theaters who helped us by collecting samples.

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Authors and Affiliations

  1. Department of Rheumatology, Beijing Hospital, National Center of Gerontology, No. 1 Da Hua Road, Dong Dan, Beijing, 100730, People’s Republic of China

    Like Zhao, Qian Wang, Chunmei Zhang & Cibo Huang

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  1. Like Zhao
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  2. Qian Wang
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  3. Chunmei Zhang
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  4. Cibo Huang
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Correspondence to Like Zhao.

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This study was funded by grants from the National Natural Science Foundation of China (No. 81102269).

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Zhao, L., Wang, Q., Zhang, C. et al. Genome-wide DNA methylation analysis of articular chondrocytes identifies TRAF1, CTGF, and CX3CL1 genes as hypomethylated in osteoarthritis. Clin Rheumatol 36, 2335–2342 (2017). https://doi.org/10.1007/s10067-017-3667-9

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  • DOI: https://doi.org/10.1007/s10067-017-3667-9

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