Manokawinchoke Jeeranan, Ritprajak Patcharee, Osathanon Thanaphum, Pavasant Prasit
Mineralized Tissue Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Henri-Dunant Rd., Pathumwan, Bangkok, 10330, Thailand.
Odontology. 2016 Jan;104(1):10-8. doi: 10.1007/s10266-014-0178-x. Epub 2014 Sep 26.
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.
雌激素缺乏与炎症相关性根尖周骨吸收增加有关。本研究旨在评估雌激素对人牙髓细胞（HDPs）中骨保护素（OPG）和核因子κB受体激活剂配体（RANKL）表达的影响及其细胞内机制。用浓度为0.1 - 10 μM的雌二醇处理HDPs。结果表明，雌二醇以剂量依赖性方式诱导OPG在mRNA和蛋白质水平上的表达。然而，未观察到对RANKL表达有影响。雌激素受体（ER）抑制剂未能减弱雌二醇诱导的OPG表达。此外，ER-α和ER-β激动剂并未模拟雌二醇对HDPs中OPG表达的作用。然而，在用雌二醇 - 牛血清白蛋白缀合物或GPR30激动剂处理的HDPs中观察到显著的OPG上调。ERK抑制剂显著增强了雌二醇诱导的OPG表达，而p38抑制剂则明显减弱了这种表达。总之，HDPs中OPG的表达可能受雌二醇与膜受体结合以及ERK和p38信号通路之间平衡的调节。
