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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Musculoskeletal Disorders 1/2015

Genome-wide DNA methylation study of hip and knee cartilage reveals embryonic organ and skeletal system morphogenesis as major pathways involved in osteoarthritis

Zeitschrift:
BMC Musculoskeletal Disorders > Ausgabe 1/2015
Autoren:
Erfan Aref-Eshghi, Yuhua Zhang, Ming Liu, Patricia E. Harper, Glynn Martin, Andrew Furey, Roger Green, Guang Sun, Proton Rahman, Guangju Zhai
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12891-015-0745-5) contains supplementary material, which is available to authorized users.
Roger Green deceased.

Competing interest

The authors do not have any competing interest to declare.

Authors’ contribution

Study Design: EA, GZ; Data collection: EA, ML, PH, GM, AF, GZ; Statistical analysis: EA, YZ, GZ; Interpretation of the results: EA, GM, AF, RG, GS, PR, GZ; Manuscript writing: EA, GZ; Critical comments on the manuscript: GM, AF, RG, GS, PR. All authors read and approved the final manuscript.

Authors’ information

Roger Green died August 9th, 2015.

Abstract

Background

Evidence suggests that epigenetics plays a role in osteoarthrits (OA). The aim of the study was to describethe genome wide DNA methylation changes in hip and knee OA and identify novel genes and pathwaysinvolved in OA by comparing the DNA methylome of the hip and knee osteoarthritic cartilage tissues withthose of OA-free individuals.

Methods

Cartilage samples were collected from hip or knee joint replacement patients either due to primary OA or hip fractures as controls. DNA was extracted from the collected cartilage and assayed by Illumina Infinium HumanMethylation450 BeadChip array, which allows for the analysis of >480,000 CpG sites. Student T-test was conducted for each CpG site and those sites with at least 10 % methylation difference and a p value <0.0005 were defined as differentially methylated regions (DMRs) for OA. A sub-analysis was also done for hip and knee OA separately. DAVID v6.7 was used for the functional annotation clustering of the DMR genes. Clustering analysis was done using multiple dimensional scaling and hierarchical clustering methods.

Results

The study included 5 patients with hip OA, 6 patients with knee OA and 7 hip cartilage samples from OA-free individuals. The comparisons of hip, knee and combined hip/knee OA patients with controls resulted in 26, 72, and 103 DMRs, respectively. The comparison between hip and knee OA revealed 67 DMRs. The overall number of the sites after considering the overlaps was 239, among which 151 sites were annotated to 145 genes. One-fifth of these genes were reported in previous studies. The functional annotation clustering of the identified genes revealed clusters significantly enriched in skeletal system morphogenesis and development. The analysis revealed significant difference among OA and OA-free cartilage, but less different between hip OA and knee OA.

Conclusions

We found that a number of CpG sites and genes across the genome were differentially methylated in OA patients, a remarkable portion of which seem to be involved in potential etiologic mechanisms of OA. Genes involved in skeletal developmental pathways and embryonic organ morphogenesis may be a potential area for further OA studies.
Zusatzmaterial
Additional file 1: Table S1. CpG sites differentially methylated in knee/hip OA compared to healthy cartilage*. Table 2. The genes and CpG sites commonly reported between our study and previous epigenome-wide studies of OA. (DOCX 36 kb)
12891_2015_745_MOESM1_ESM.docx
Literatur
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