Dataset Information

Influence of DNA methylation on the expression of OPG/RANKL in primary osteoporosis.

ABSTRACT: Purpose: A key factor in regulating bone absorption is the proportion of RANKL/OPG. Although many reports showing diverse transcription factors or epigenetic modification could be responsible for regulating RANKL&OPG ratio, there is still little exploration on promoter methylation status of both genes in osteoporotic bone tissues. Our aim is to investigate the changes of methylation in CpG island of these genes' promoters in patients with primary osteoporosis. Methods: The diagnosis of osteoporosis was based on the results of dual energy X-ray absorptiometry measurements. All femoral bone tissues were separated in surgeries. After extracting total RNA, we checked the relative expression levels of OPG and RANKL by quantitative real time PCR. The genomic DNA of Non-OPF (Non-osteoporotic fracture bone tissues) & OPF (osteoporotic fracture bone tissues) were treated by bisulfite modification, and methylation status of CpG sites in the CpG island of OPG/RANKL promoters were determined by DNA sequencing. Results: RANKL expression in the OPF group was significantly higher than that in Non-OPF group, and the CpG methylation status in RANKL gene promoter was significantly lower. However, for OPG, lower gene expression level and higher methylation degree were found in the OPF group. Conclusion: Our study demonstrated that DNA methylation influenced the transcriptional expression of OPG and RANKL, which probably take on a "main switch" role in pathogenesis of primary osteoporosis.

SUBMITTER: Wang P

PROVIDER: S-EPMC6216050 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Influence of DNA methylation on the expression of OPG/RANKL in primary osteoporosis.

Wang Peng P Cao Yanming Y Zhan Dongxiang D Wang Ding D Wang Bin B Liu Yamei Y Li Gang G He Wei W Wang Haibin H Xu Liangliang L

International journal of medical sciences 20181003 13

<b>Purpose:</b> A key factor in regulating bone absorption is the proportion of RANKL/OPG. Although many reports showing diverse transcription factors or epigenetic modification could be responsible for regulating RANKL&OPG ratio, there is still little exploration on promoter methylation status of both genes in osteoporotic bone tissues. Our aim is to investigate the changes of methylation in CpG island of these genes' promoters in patients with primary osteoporosis. <b>Methods:</b> The diagnosi ...[more]

PMID: 30443169

Similar Datasets

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

Project description:The pathogenesis of periodontitis involves a complex interaction between the microbial challenge and the host immune response. The individual immunoinflammatory response has a great contribution in the pathogenesis of the disease and becomes a trigger in the process of bone remodeling which is a characteristic of the disease. Thus, the aim of this study was to evaluate the influence of the TLR4 A896G (rs4986790), TLR4 C1196T (rs4986791), CD14 C-260T (rs2569190), RANKL (TNFSF11, rs2277438), and OPG (TNFSF11B C163T, rs3102735) polymorphisms in periodontitis. A case-control study was conducted on patients with periodontitis (N = 203) and controls (N = 213) over 30 years of age, without diabetes mellitus, acute infections, and osteoarthritis, and patients without aggressive periodontitis, i.e., stage IV and C degree of periodontitis, and any periodontal treatment performed in the last 6 months. Genotypes were determined by the PCR-RFLP and sequencing method. The frequency comparisons between case and controls were performed using the chi-square test and logistic regression (OpenEpi and SNPStats software). The risk (OR) was evaluated for values of P < 0.05. Differences in TLR4, CD14, RANKL, and OPG genotype and allele frequency distributions were not observed between patients and controls. However, some variants were a risk factor for the development of periodontitis when considering gender and smoking habits. The TLR4 896 A/G genotype was a risk factor for periodontitis in males (OR = 2.86), and the TLR4 1196C/C genotype was a risk factor for nonsmoking males (OR = 1.85) when compared to women. The RANKL A/A and the OPG T/C genotype was associated with the risk of the disease in nonsmoking men compared to nonsmoking women with the same genotype (OR = 1.96 and OR = 2.9, respectively). In conclusion, TLR4, CD14, RANKL, and OPG variants were not associated with periodontitis. However, TLR4, RANKL, and OPG polymorphisms could be a risk for periodontitis in males regardless of smoking habits.

Dataset Information

Influence of DNA methylation on the expression of OPG/RANKL in primary osteoporosis.

Publications

Influence of DNA methylation on the expression of OPG/RANKL in primary osteoporosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets