Preliminary investigation on the molecular mechanisms underlying the correlation between VDR-FokI genotype and periodontitis.

Abstract

The only polymorphism that could change the protein structure in vitamin D receptor (VDR) is the FokI polymorphism (rs2228570). The FF genotype has the strongest transcriptional activity of VDR and is correlated with higher susceptibility to periodontitis. To reveal the possible molecular mechanisms for the correlation preliminarily, the influence of VDR-FokI genotype on the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) in human gingival fibroblasts (hGFs) and human periodontal ligament cells (hPDLCs) was investigated in this study. hGFs and hPDLCs from 15 donors (five FF, seven Ff, and three ff) were treated with 1,25OH2 D3 , with or without the specific knockdown of VDR using siRNA. The mRNA and protein expression of OPG and RANKL were detected using real-time PCR and enzyme-linked immunosorbent assay, respectively. Both in hGFs and hPDLCs, 1,25OH2 D3 could significantly induce the mRNA and protein expression of RANKL, and FF genotype had significantly higher induction than the other genotypes, however, neither 1,25OH2 D3 nor VDR-FokI had significant influence on the OPG expression. As a result, the RANKL/OPG ratio was significantly elevated under 1,25OH2 D3 stimulation and FF genotype had the most remarkable elevation. When VDR was knocked down, all the differences among the three genotypes disappeared. The strongest transcriptional activity of FF genotype might contribute to the strongest enhancement of RANKL expression and RANKL/OPG ratio in hGFs and hPDLCs stimulated by 1,25OH2 D3 , which might help to reveal the mechanisms of the correlation between FF genotype and susceptibility to periodontitis.