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Bone Abstracts (2016) 5 P233 | DOI: 10.1530/boneabs.5.P233

University of Cantabria, IDIVAL, Santander, Spain.

Osteoporosis (OP) is characterised by reduced bone mass, due to an insufficient osteoblast-mediated bone formation, unable to replace the bone tissue removed by osteoclasts. Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into osteoblasts, adipocytes and chondrocytes. Epigenetic marks like DNA methylation could influence the differentiation potential of these cells into osteoblasts and, consequently, the risk of OP. To explore this hypothesis, we analysed the methylome and the transcriptome of MSCs derived from patients with osteoporotic hip fractures (OP) and control individuals with osteoarthritis (OA).

MSCs were obtained from the femoral bone marrow (n=20) and their nature confirmed by the expression of surface markers and the ability to differentiate into osteoblasts and adipocytes. DNA methylation was analysed with the HumanMethylation450K Bead Chip (Illumina®); RNA transcripts were analysed by NGS.

MSCs from patients with osteoporotic fractures showed 4417 hypermethylated and 4621 hypomethylated CpG sites, in comparison with OA. Of these, there were 40 differentially methylated regions (DMRs) located at CpG islands, 217 located at promoters, 129 located at gene bodies and 1684 located at gene enhancer regions. Enhancer DMRs were associated with genes that were over-represented in several bone-related pathways, like the Wnt pathway or osteoblast differentiation and ossification pathways.

The RNAseq analysis showed 174 genes significantly over-expressed and 355 under-expressed in fractures in comparison with OA. Many differentially expressed genes were also associated with DMRs at their enhancers. In fact, 30 genes overexpressed in fractures showed enhancer’s DMRs (14 hypermethylated, 16 hypomethylated). On the other hand, 67 under-expressed genes had DMRs (48 hypermethylated and 19 hypomethylated).

In conclusion, we found a number of DMRs (mainly in enhancer regions) in MSCs of patients with OP and OA that are likely to influence their capability to differentiate into bone forming cells. Validation experiments are underway.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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