Role of GSα-dependent signaling in bone homeostasis, condylar remodeling and enamel mineralization
OA Version
Citation
Abstract
The Dentin Matrix Protein (DMP1) is a critical regulator of bone and dentin mineralization and this protein is highly expressed in osteocytes and odontoblasts. Gs alpha (Gsα) protein, the main intracellular signal of a broad class of G-protein coupled receptors (GPCRs), is highly expressed in bone cells, including osteocytes. We and others have demonstrated that mice lacking the Gsα expression, predominantly in osteocytes (DMP1-GsαKO mice), develop severe osteopenia driven by a marked reduction in osteoblast activity associated with a significant increase in SOST/sclerostin expression. In this study, we have examined the role of Gsα in the jaws and teeth of DMP1-GsαKO mice to investigate if the absence of Gsα expression in osteocytes and odontoblasts altered teeth and jaws morphology. Our previous studies showed that DMP1-GsαKO leads to a significant decrease in both trabecular and cortical bone content in the skeleton, as assessed by μCT and histomorphometric analysis. Here we characterize the dental and craniofacial phenotype of DMP1-GsαKO mice. Results showed that DMP1-GsαKO had decreased total mandibular bone mineral density (BMD), total mandibular mineral content (BMC), condylar BMD and total tooth mineralization as assessed by DEXA using a Lunar PIXImus II densitometer.
Furthermore, μCT analysis revealed that condylar bone volume and tooth mineralization is reduced in DMP1-GsαKO mice compared to control littermate. μCT also showed that the overall skull size and specifically the zygomatic bone is larger in the control group. Next, we examined H&E histological sections of the jaws of DMP1-GsαKO and control mice, which confirmed the osteopenic phenotype. Tartrate-resistant acid phosphatase (TRAP) staining showed that the number of TRAP-positive osteoclasts was increased in the DMP1-GsαKO mice compared to controls, suggesting increased bone resorption. In conclusion, our studies identified Gsa signaling in osteocytes and odontoblasts as important in maintaining normal bone and tooth homeostasis.