Genetic polymorphisms influence gene expression of human periodontal ligament fibroblasts in the early phases of orthodontic tooth movement.

Abstract

Genetic polymorphisms could be involved in the individual rate of OTM (orthodontic tooth movement) corresponding to the clinical phenomenon of "slow movers" and "fast movers". This study evaluated, if genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6 are associated with the expression of RANKL, OPG, COX2 and IL6 by human periodontal ligament (hPDL) fibroblasts during OTM. Primary hPDL fibroblasts from periodontal connective tissue of teeth extracted from 57 human subjects for medical reasons were collected, isolated, cultivated and characterized. To simulate orthodontic forces in PDL pressure areas, a physiological compressive force of 2 g/cm2 was applied to the hPDL fibroblasts under cell culture conditions at 70% confluency for 48h, using a glass disc. Thereafter we analysed relative expression of RANKL, OPG, COX2 and IL6 by RT-qPCR. We also performed genotyping analysis of seven genetic polymorphisms in RANK, RANKL, OPG, COX2 and IL6. Relative gene expression was compared among the genotypes. The genotype TT in polymorphism rs9594738 (RANKL) had a higher RANKL expression in the recessive model (p = 0.021; TT vs. CT + CC). For polymorphism rs9594738 (RANKL), in the recessive model, TT was associated with a higher RANKL/OPG expression ratio (p = 0.013; TT vs. CT + CC). In the dominant model, GG genotype in rs5275 (COX2) was associated with a lower gene expression of COX2 (p = 0.04; GG vs. AA + AG). Genetic polymorphisms in genes associated with OTM affect the relative force-induced upregulation of these genes in hPDL fibroblasts.