Gsα Deficiency in Osteocytes Alters Craniofacial Growth and Enamel Mineralisation.

INTRODUCTION

Osteocytes express numerous G protein-coupled receptors (GPCRs) and mice lacking the stimulatory subunit of G-protein (Gsα) in osteocytes (DMP1-GsαKO mice) have severe osteopenia. We previously demonstrated that the severe osteopenia in these mice was mediated by increased sclerostin expression, which suppresses osteoblast functions. In this study we analyse both the craniofacial and tooth characteristics of these mutant mice.

METHODS

A total of 28, 6-8-week-old mice were used (Gsα fl/fl or Control, DMP1-Cre;Gsα fl/fl or DMP1-GsαKO). Total bone mineral density (BMD), total bone mineral content (BMC), condyles' BMD and incisor mineralisation were quantitatively assessed by DEXA. Bone microarchitecture of the mandible and full head of mice was quantitatively assessed with high-resolution micro-computed tomography (μCT). For the condylar region, we assessed total BMD and bone volume fraction (BV/TV, %). Three linear measurements of the mandible were measured: mandibular length, condyle head length and condyle head width, and samples were assessed by histomorphometric analysis.

RESULTS

DMP1-GsαKO mice have decreased total mandibular BMD, total mandibular BMC, condylar BMD and total tooth mineralisation as assessed by DEXA. μCT analysis revealed that condylar bone volume and tooth mineralisation were reduced in DMP1-GsαKO mice and showed that skull size and specifically the zygomatic bone were larger in control. H&E histological sections of the jaws of DMP1-GsαKO mice 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.

CONCLUSION

Our studies identified Gsα signalling in osteocytes, mature osteoblasts and odontoblasts, as important in maintaining normal bone and tooth homeostasis.