Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis

Jesus Delgado-Calle, Agustín F. Fernández, Jesús Sainz, María T. Zarrabeitia, Carolina Sañudo, Raúl García-Renedo, María I. Pérez-Núñez, Carmen García-Ibarbia, Mario F. Fraga, José A. Riancho

Research output: Contribution to journalArticle

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Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)197-205
Number of pages9
JournalArthritis and Rheumatism
Volume65
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

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Osteoarthritis
Methylation
Osteoporosis
Genome
Bone and Bones
Genes
Hip Osteoarthritis
Data Mining
Homeobox Genes
Hip Fractures
Cell Differentiation
Osteoporotic Fractures
Genome-Wide Association Study
Thigh
Transcriptome
Quality Control
Embryonic Development
Glycoproteins
Transcription Factors
Software

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Delgado-Calle, J., Fernández, A. F., Sainz, J., Zarrabeitia, M. T., Sañudo, C., García-Renedo, R., ... Riancho, J. A. (2013). Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis. Arthritis and Rheumatism, 65(1), 197-205. https://doi.org/10.1002/art.37753

Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis. / Delgado-Calle, Jesus; Fernández, Agustín F.; Sainz, Jesús; Zarrabeitia, María T.; Sañudo, Carolina; García-Renedo, Raúl; Pérez-Núñez, María I.; García-Ibarbia, Carmen; Fraga, Mario F.; Riancho, José A.

In: Arthritis and Rheumatism, Vol. 65, No. 1, 01.2013, p. 197-205.

Research output: Contribution to journalArticle

Delgado-Calle, J, Fernández, AF, Sainz, J, Zarrabeitia, MT, Sañudo, C, García-Renedo, R, Pérez-Núñez, MI, García-Ibarbia, C, Fraga, MF & Riancho, JA 2013, 'Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis', Arthritis and Rheumatism, vol. 65, no. 1, pp. 197-205. https://doi.org/10.1002/art.37753
Delgado-Calle, Jesus ; Fernández, Agustín F. ; Sainz, Jesús ; Zarrabeitia, María T. ; Sañudo, Carolina ; García-Renedo, Raúl ; Pérez-Núñez, María I. ; García-Ibarbia, Carmen ; Fraga, Mario F. ; Riancho, José A. / Genome-wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis. In: Arthritis and Rheumatism. 2013 ; Vol. 65, No. 1. pp. 197-205.
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abstract = "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 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.",
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AU - Sañudo, Carolina

AU - García-Renedo, Raúl

AU - Pérez-Núñez, María I.

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AU - Fraga, Mario F.

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N2 - 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 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.

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