Format

Send to

Choose Destination
Osteoarthritis Cartilage. 2017 Dec;25(12):2127-2133. doi: 10.1016/j.joca.2017.08.002. Epub 2017 Aug 14.

Genome-wide DNA methylation profiling of articular cartilage reveals significant epigenetic alterations in Kashin-Beck disease and osteoarthritis.

Author information

1
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.
2
School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: yuyan@xjtu.edu.cn.
3
School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
4
Osteonecrosis and Joint Reconstruction Ward, Department of Joint Surgery, HongHui Hospital, Health Science Center, Xi'an Jiaotong University, PR China.
5
Department of Orthopedics, Second Affiliated Hospital of Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
6
School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, PR China. Electronic address: fzhxjtu@xjtu.edu.cn.

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.

KEYWORDS:

Cartilage; DNA methylation profile; Kashin-Beck disease; Osteoarthritis

PMID:
28818737
DOI:
10.1016/j.joca.2017.08.002
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center