Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis
Jesús Delgado-Calle
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Search for more papers by this authorAgustín F. Fernández
Instituto Universitario de Oncología del Principado de Asturias, HUCA, and University of Oviedo, Oviedo, Spain
Search for more papers by this authorJesús Sainz
Institute of Biomedicine and Biotechnology of Cantabria, and Spanish Research Council, Santander, Spain
Search for more papers by this authorCarolina Sañudo
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Search for more papers by this authorMaría I. Pérez-Núñez
Hospital U. M. Valdecilla, Santander, Spain
Search for more papers by this authorCarmen García-Ibarbia
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Search for more papers by this authorMario F. Fraga
Instituto Universitario de Oncología del Principado de Asturias, HUCA, and University of Oviedo, Oviedo, Spain
Search for more papers by this authorCorresponding Author
José A. Riancho
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Departamento de Medicina Interna, Hospital U. M. Valdecilla, Avenida Valdecilla s/n, 39011 Santander, SpainSearch for more papers by this authorJesús Delgado-Calle
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Search for more papers by this authorAgustín F. Fernández
Instituto Universitario de Oncología del Principado de Asturias, HUCA, and University of Oviedo, Oviedo, Spain
Search for more papers by this authorJesús Sainz
Institute of Biomedicine and Biotechnology of Cantabria, and Spanish Research Council, Santander, Spain
Search for more papers by this authorCarolina Sañudo
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Search for more papers by this authorMaría I. Pérez-Núñez
Hospital U. M. Valdecilla, Santander, Spain
Search for more papers by this authorCarmen García-Ibarbia
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Search for more papers by this authorMario F. Fraga
Instituto Universitario de Oncología del Principado de Asturias, HUCA, and University of Oviedo, Oviedo, Spain
Search for more papers by this authorCorresponding Author
José A. Riancho
Hospital U. M. Valdecilla–Instituto de Formación e Investigación Marqués de Valdecilla, University of Cantabria, and RETICEF, Santander, Spain
Departamento de Medicina Interna, Hospital U. M. Valdecilla, Avenida Valdecilla s/n, 39011 Santander, SpainSearch for more papers by this authorAbstract
Objective
To determine genome-wide methylation profiles of bone from patients with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures.
Methods
Trabecular bone pieces were obtained from the central part of the femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA was isolated, and methylation was explored with Illumina methylation arrays. RNA was extracted, pooled, and deep-sequenced to obtain the whole transcriptome. Differentially methylated regions were identified, and connections between genes with differentially methylated regions were explored by pathway and text-mining analyses.
Results
After quality control, methylation of 23,367 CpG sites (13,463 genes) was analyzed. There was a genome-wide inverse relationship between methylation and gene expression in both patient groups. Comparison of OP and OA bones revealed 241 CpG sites, located in 228 genes, with significant differences in methylation (false discovery rate <0.05). Of them, 217 were less methylated in OP than in OA. The absolute methylation differences were >5% in 128 CpG sites and >10% in 45 CpG sites. The differentially methylated genes were enriched for association with bone traits in the genome-wide association study catalog. Pathway analysis and text-mining analysis with Gene Relationships Across Implicated Loci software revealed enrichment in genes participating in glycoprotein metabolism or cell differentiation, and particularly in the homeobox superfamily of transcription factors.
Conclusion
Genome-wide methylation profiling of bone samples revealed differentially methylated regions in OP and OA. These regions were enriched in genes associated with cell differentiation and skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the existence of a developmental component in the predisposition to these disorders.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| ART_37753_sm_SupplTable1.doc509.5 KB | Supplementary Table 1 |
| ART_37753_sm_SupplTable2.doc104 KB | Supplementary Table 2 |
| ART_37753_sm_SupplFig1.tif16.2 MB | Supplementary Figure 1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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