The Role of Estrogen Receptor-β mediating Signaling in Odontogenesis

Objectives: Estrogen receptor beta (ER-β) has shown to play a role in the osteogenic differentiation of human dental pulp stem cells (hDPCs) and a regulatory role in bone turnover by contributing inhibitory effects to the bone-forming role of estrogen receptor alpha (ER-α). Little knowledge exists to the extent ER-β mediates the processes of odontogenesis and its differing role between genders. The goal of this study was to determine the role of ER-β in mediating the actions of estrogen in odontoblast, dentin, enamel and alveolar bone development/formation.
Methods: ER-β was deleted in odontoblasts (ER-βcKO) by crossing ER-β^fl/fl mice with Dmp-1-Cre-Positive mice. Dmp-1-Cre-Negative littermates served as controls. We analyzed males and females separately (n=4/group). At 6-months of age, mice were euthanized and mandibles were dissected and processed as needed: right half mandibles were embedded in PMMA resin for MicroCT measurement of cementoenamel junction to alveolar bone crest (CEJ-ABC) height. Resin embedded acid etched scanning electron microscope (SEM) imaging was also performed. Left half mandibles were demineralized and embedded in paraffin for histological analysis via H&E and TRAP staining. Data was analyzed using a two-tailed unpaired t-test.
Results: CEJ-ABC heights were significantly decreased in ER-βcKO male mice when compared to controls (p<0.05). Female mice showed no differences. Female ER-βcKO mice displayed an increased amount of dentin tubule branching (149±9 vs. 107±15) (n=2) whereas the male ER-βcKO mice displayed fewer when compared to controls (88.5±10.5 vs. 135±3) (n=2).
Conclusions: The results suggest that deletion of ER-β increases alveolar bone formation and decreases dentin tubule branching in male mice. Deletion of ER-β in females increases dentin tubule branching only. These findings demonstrate an important role for ER-β in jaw and tooth development which is different in males and females. Funded by UMKC SOD Summer Scholars program.