Role of DNA methylation in the regulation of the RANKL-OPG system in human bone

• DOI: 10.4161/epi.7.1.18753
• Publication Date: 2012-01-25T19:58:00Z
• Authors: Jesús Delgado-Calle; Carolina Sañudo; Agustín F. Fernández; Raúl García-Renedo; Mario F. Fraga; José A. Riancho
• Keywords: Bisulfite sequencing; CpG site; Demethylating agent

Osteoblasts are specialized cells that form new bone and also indirectly influence resorption by producing factors modulate osteoclast differentiation. Although the methylation of CpG islands plays an important role in regulation gene expression, there is still scanty information about its human bone. The aim this study was to investigate on transcriptional levels two osteoblast-derived critical osteoclastogenesis: receptor activator nuclear factor NF-κB ligand (RANKL) soluble decoy osteoprotegerin (OPG). Quantitative specific PCR (qMSP) pyrosequencing analysis various cell types showed regulatory regions these genes, vicinity transcription start sites, repressed transcription, whereas active associated with low methylation. In addition, treatment DNA demethylating agent 5-azadeoxycitidine promoted a 170-fold induction RANKL 20-fold OPG mRNA expression HEK-293 cells, which hypermethylation barely expressed transcripts at baseline. Transcriptional both genes were explored tissue samples from patients hip fractures osteoarthritis. transcript abundance RANKL:OPG ratio significantly higher than those osteoarthritis (RANKL: 0.76 ± 0.23 vs. 0.24 0.08, p = 0.012; RANKL/OPG: 7.66 2.49 0.92 0.21, 0.002), no evidence for differential across patient groups. conclusion, association between repression strongly suggests methylation-dependent mechanisms play osteoclastogenesis. However, other appear be involved increased RANKL/OPG osteoporotic fractures.