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Genome-wide DNA methylation profiling of articular cartilage reveals significant epigenetic alterations in Kashin-Beck disease and osteoarthritis.
Osteoarthritis Cartilage. 2017 12; 25(12):2127-2133.OC

Abstract

OBJECTIVE

To determine genome-wide DNA methylation profiles of knee cartilage from patients with Kashin-Beck disease (KBD) and osteoarthritis (OA).

METHOD

Knee cartilage was collected from 14 grade III KBD patients, 5 primary OA patients and 13 healthy subjects. The genome-wide methylation profiles of 5 KBD cartilage, 5 OA cartilage and 5 normal cartilage were determined by Illumina HumanMethylation450 array. Illumina Methylation Analyzer package was employed for identifying differentially methylated CpG sites. Functional annotation and enrichment analysis of differentially methylated genes (DMG) were conducted using GeneRIF database, Ingenuity Pathway Analysis (IPA) and The Database for Annotation, Visualization and Integrated Discovery (DAVID). Mass spectrometry (MS) and immunohistochemistry (IHC) were conducted to validate the functional relevance of identified KBD associated gene.

RESULTS

We identified a total of 1212 differentially methylated CpG sites in KBD vs Normal, annotated to 264 hypermethylated and 368 hypomethylated genes. Comparing the DNA methylation profiles of KBD vs Normal and OA vs Normal detected overlap of 367 differentially methylated CpG sites (annotated to 182 genes) as well as 845 KBD-specific differentially methylated CpG sites (annotated to 471 unique genes). MS and IHC confirmed the hypermethylation status and decreased protein expression of HAPLN1 gene in KBD cartilage.

CONCLUSION

Our data implicate epigenetic dysregulation of a host of genes in KBD and OA. Furthermore, we observed common causal epigenetic changes shared by KBD and OA.

Authors+Show Affiliations

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: yuyan@xjtu.edu.cn.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China.Osteonecrosis and Joint Reconstruction Ward, Department of Joint Surgery, HongHui Hospital, Health Science Center, Xi'an Jiaotong University, PR China.Department of Orthopedics, Second Affiliated Hospital of Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.Department of Orthopedics, Second Affiliated Hospital of Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, PR China.School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: fzhxjtu@xjtu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28818737

Citation

Wang, W, et al. "Genome-wide DNA Methylation Profiling of Articular Cartilage Reveals Significant Epigenetic Alterations in Kashin-Beck Disease and Osteoarthritis." Osteoarthritis and Cartilage, vol. 25, no. 12, 2017, pp. 2127-2133.
Wang W, Yu Y, Hao J, et al. Genome-wide DNA methylation profiling of articular cartilage reveals significant epigenetic alterations in Kashin-Beck disease and osteoarthritis. Osteoarthr Cartil. 2017;25(12):2127-2133.
Wang, W., Yu, Y., Hao, J., Wen, Y., Han, J., Hou, W., Liu, R., Zhao, B., He, A., Li, P., Fan, Q., Wu, C., Wang, S., Wang, X., Ning, Y., Guo, X., & Zhang, F. (2017). Genome-wide DNA methylation profiling of articular cartilage reveals significant epigenetic alterations in Kashin-Beck disease and osteoarthritis. Osteoarthritis and Cartilage, 25(12), 2127-2133. https://doi.org/10.1016/j.joca.2017.08.002
Wang W, et al. Genome-wide DNA Methylation Profiling of Articular Cartilage Reveals Significant Epigenetic Alterations in Kashin-Beck Disease and Osteoarthritis. Osteoarthr Cartil. 2017;25(12):2127-2133. PubMed PMID: 28818737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide DNA methylation profiling of articular cartilage reveals significant epigenetic alterations in Kashin-Beck disease and osteoarthritis. AU - Wang,W, AU - Yu,Y, AU - Hao,J, AU - Wen,Y, AU - Han,J, AU - Hou,W, AU - Liu,R, AU - Zhao,B, AU - He,A, AU - Li,P, AU - Fan,Q, AU - Wu,C, AU - Wang,S, AU - Wang,X, AU - Ning,Y, AU - Guo,X, AU - Zhang,F, Y1 - 2017/08/14/ PY - 2017/02/23/received PY - 2017/06/26/revised PY - 2017/08/04/accepted PY - 2017/8/19/pubmed PY - 2018/7/19/medline PY - 2017/8/19/entrez KW - Cartilage KW - DNA methylation profile KW - Kashin-Beck disease KW - Osteoarthritis SP - 2127 EP - 2133 JF - Osteoarthritis and cartilage JO - Osteoarthr. Cartil. VL - 25 IS - 12 N2 - OBJECTIVE: To determine genome-wide DNA methylation profiles of knee cartilage from patients with Kashin-Beck disease (KBD) and osteoarthritis (OA). METHOD: Knee cartilage was collected from 14 grade III KBD patients, 5 primary OA patients and 13 healthy subjects. The genome-wide methylation profiles of 5 KBD cartilage, 5 OA cartilage and 5 normal cartilage were determined by Illumina HumanMethylation450 array. Illumina Methylation Analyzer package was employed for identifying differentially methylated CpG sites. Functional annotation and enrichment analysis of differentially methylated genes (DMG) were conducted using GeneRIF database, Ingenuity Pathway Analysis (IPA) and The Database for Annotation, Visualization and Integrated Discovery (DAVID). Mass spectrometry (MS) and immunohistochemistry (IHC) were conducted to validate the functional relevance of identified KBD associated gene. RESULTS: We identified a total of 1212 differentially methylated CpG sites in KBD vs Normal, annotated to 264 hypermethylated and 368 hypomethylated genes. Comparing the DNA methylation profiles of KBD vs Normal and OA vs Normal detected overlap of 367 differentially methylated CpG sites (annotated to 182 genes) as well as 845 KBD-specific differentially methylated CpG sites (annotated to 471 unique genes). MS and IHC confirmed the hypermethylation status and decreased protein expression of HAPLN1 gene in KBD cartilage. CONCLUSION: Our data implicate epigenetic dysregulation of a host of genes in KBD and OA. Furthermore, we observed common causal epigenetic changes shared by KBD and OA. SN - 1522-9653 UR - https://www.unboundmedicine.com/medline/citation/28818737/Genome_wide_DNA_methylation_profiling_of_articular_cartilage_reveals_significant_epigenetic_alterations_in_Kashin_Beck_disease_and_osteoarthritis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1063-4584(17)31139-1 DB - PRIME DP - Unbound Medicine ER -