Effect of psychological stress on the expression of Runx2 and CCAAT/enhancer-binding protein pathways leading to orofacial and dental abnormalities

Abstract

Craniofacial and dental development results from a dynamic interplay between regulatory and structural genes and environmental factors including prenatal stress. Stress not only activates various types of cytokines, growth factors and hormones including TNF, TGF-1 and glucocorticoids but also simultaneously suppresses or activates specific regulatory pathways such as Wnt/-catenin, RANKL and ERK/MAPK; this in turn results in impaired or diminished regulation of various genes involved in craniofacial and dental development. In this study, we examined the hypothesis that prenatal stress can suppress Runx2 and C/EBP genes expression and subsequent OC and DSPP mRNA levels, the most abundant non-collagenous bone and tooth specific extracellular matrix proteins, respectively. We used 48 female Wistar rats as dams which were later paired with a sexually experienced male. Pregnant rats were assigned to either the stress (SG) or control (CG) groups. SG dams were immobilized 3 times/day for 45 minutes. We assessed Runx2, DSPP and OC at both G14 and G21 and C/EBP at G21 in the fetuses of SG and CG rats. RNA isolation and real-time PCR assay were carried out. Runx2 and C/EBP mRNA levels reduced significantly in fetuses of restrained dams compared with those of the control group (Runx2: day14, p<0.001; day21, p=0.001) (C/EBP: day21, p<0.001). OC and DSPP genes expression was also suppressed significantly in response to restraint stress (OC: day14, p=0.01; day21, p=0.004) (DSPP: day14, p=0.004; day21, p=0.03). Consequently, it could be concluded that psychological prenatal stress has a major role in suppressing the expression of bone and tooth related genes involved in bone and tooth development.