Estradiol induces osteoprotegerin expression by human dental pulp cells.

Estrogen deficiency is associated with increased inflammation related periapical bone resorption. The present study aimed to evaluate the effect and intracellular mechanism(s) of estrogen on osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) expression in human dental pulp cells (HDPs). HDPs were treated with estradiol at a concentration of 0.1-10 μM. The results showed that estradiol induced OPG expression at both the mRNA and protein levels in a dose-dependent manner. However, no influence on RANKL expression was observed. An estrogen receptor (ER) inhibitor failed to attenuate the estradiol-induced OPG expression. Furthermore, ER-α and ER-β agonists did not simulate estradiol's effects on OPG expression by HDPs. However, a significant OPG upregulation was observed in HDPs treated with an estradiol-BSA conjugate or a GPR30 agonist. An ERK inhibitor significantly enhanced estradiol-induced OPG expression, whereas a p38 inhibitor markedly attenuated this expression. In conclusion, OPG expression by HDPs may be regulated by estradiol binding a membrane receptor and the balance between the ERK and p38 signaling pathways.