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Primary osteoporosis is not reflected by disease-specific DNA methylation or accelerated epigenetic age in blood

ABSTRACT: Osteoporosis is an age-related metabolic bone disease. Hence, osteoporotic patients might suffer from molecular features of accelerated aging, which is generally reflected by specific age-associated DNA methylation (DNAm) changes. In this study, we analyzed genome wide DNAm profiles of peripheral blood from patients with manifest primary osteoporosis and non-osteoporotic controls. Statistical analysis did not reveal any individual CG dinucleotides (CpG sites) with significant aberrant DNAm in osteoporosis. Subsequently, we analyzed if age-associated DNAm patterns are increased in OP. Using three independent age-predictors we did not find any evidence for accelerated epigenetic age in blood of osteoporotic patients. Taken together, osteoporosis is not reflected by characteristic DNAm patterns of peripheral blood that might be used as biomarker for the disease. The prevalence of osteoporosis is age-associated – but it is not associated with premature epigenetic aging in peripheral blood.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99624 | GEO | 2018/03/13

REPOSITORIES: GEO

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Project description:Large-scale transcriptional profiling has enormous potential for discovery of osteoporosis susceptibility genes and for identification of the molecular mechanisms by which these genes and associated pathways regulate bone maintenance and turnover. A potential challenge in the use of this method for the discovery of osteoporosis genes is the difficulty of obtaining bone tissue samples from large numbers of individuals. In this study, we tested the applicability of using peripheral blood mononuclear cell (PBMC)-derived transcriptional profiles as a surrogate to cortical bone transcriptional profiles to address questions of skeletal genetics. We used a well-established and genetically well-characterized nonhuman primate model for human bone maintenance and turnover. We determined that a high degree of overlap exists in gene expression of cortical bone and PBMCs and that genes in both the osteoporosis-associated RANK Osteoclast and Estrogen Receptor Signaling pathways are highly expressed in PBMCs. Genes within the Wnt Signaling pathway, also implicated in osteoporosis pathobiology, are expressed in PBMCs, albeit to a lesser extent. These results are the first in an effort to comprehensively characterize the relationship between the PBMC transcriptome and bone M-bM-^@M-^S knowledge that is essential for maximizing the use of PBMCs to identify genes and signaling pathways relevant to osteoporosis pathogenesis. It is also a first step in identifying genes that correlate in a predictable manner between PBMCs and cortical bone from healthy and osteoporotic individuals, potentially allowing us to identify genes that could be used to diagnose osteoporosis prior to detectible bone loss and with easily obtained PBMCs. Total RNA was isolated from peripheral blood mononuclear cells and cortical bone of a nonhuman primate model (Papio hamadryas ssp.) of bone maintenance and turnover. Both samples were taken from the same animal. Tissue from 15 animals was used for the study.

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Primary osteoporosis is not reflected by disease-specific DNA methylation or accelerated epigenetic age in blood

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