Respective role of membrane and nuclear estrogen receptor (ER) ? in the mandible of growing mice: Implications for ER? modulation.

ABSTRACT: Estrogens play an important role in bone growth and maturation as well as in the regulation of bone turnover in adults. Although the effects of 17?-estradiol (E2) are well documented in long bones and vertebrae, little is known regarding its action in the mandible. E2 actions could be mediated by estrogen receptor (ER) ? or ?. ERs act primarily as transcriptional factors through two activation functions (AFs), AF1 and AF2, but they can also elicit membrane-initiated steroid signaling (MISS). The aim of the present study was to define ER pathways involved in E2 effects on mandibular bone. Using mice models targeting ER? or ER?, we first show that E2 effects on mandibular bone are mediated by ER? and do not require ER?. Second, we show that nuclear ER?AF2 is absolutely required for all the actions of E2 on mandibular bone. Third, inactivation of ER?MISS partially reduced the E2 response on bone thickness and volume, whereas there was no significant impact on bone mineral density. Altogether, these results show that both nuclear and membrane ER? are requested to mediate full estrogen effects in the mandible of growing mice. Finally, selective activation of ER?MISS is able to exert an effect on alveolar bone but not on the cortical compartment, contrary to its protective action on femoral cortical bone. To conclude, these results highlight similarities but also specificities between effects of estrogen in long bones and in the mandible that could be of interest in therapeutic approaches to treat bone mass reduction. © 2018 American Society for Bone and Mineral Research.

SUBMITTER: Vinel A 

PROVIDER: S-EPMC6563159 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature