UCSF

Objectives: In this study, orthodontic tooth movement (OTM) was applied to TβRIIocy-/- mice to elucidate the role of osteocyte-intrinsic TGFβ signaling in alveolar bone remodeling during tooth movement.Methods: Osteocyte-specific TGFβ receptor II knockout mice were examined to study whether TGFβ signaling in osteocytes is required for alveolar bone remodeling induced by orthodontic tooth movement forces. Male and female mice underwent OTM appliance delivery under general anesthesia. OTM was induced by a coil spring appliance that was ligated and bonded to the maxillary left first molar and the maxillary incisors. The mice underwent OTM for 14 days until euthanized. Then ex-vivo MicroCT was used to measure OTM, bone mineral density, bone volume fraction, and bone to tissue volume ratio. The study included eight groups of mice: male and female control (CTRL), and male and female knockout (KO) in Dmp1-Cre+/-;Tbr2fl/fl group and Dmp1-Cre-/-;Tbr2fl/fl groups. Control mice also underwent ex-vivo MicroCT and was used to measure bone mineral density, bone volume fraction, and bone to tissue volume ratio for comparison. Results: Our results shed light on some striking differences between genders as well as the properties of alveolar bone versus the reported properties of long bone in the literature. Non-experimental baseline group (no OTM) there was no statistically significant difference in bone quality between genotypes within the same gender. However, at baseline there was a statistically significant difference in alveolar bone quality between females and males. We found utilizing orthodontic tooth movement linear measurements that there was a large variation in OTM in the male Dmp1-Cre+/-;Tbr2fl/fl group, which could be explained by the disruption of the down signaling cascade when TGFβ is not functioning. Also, in males we found a decreased BV/TV and BMD in alveolar bone in the OTM group compared to the gender-matched controls. Conclusions: This study furthers our understanding of the role osteocytes may play in the process of bone remodeling during OTM. Our preliminary data were promising and increasing the sample size will help support further scientific discovery and clinical applications. The OTM mouse model utilized in this study is reliable and reproducible for long term studies. The significant differences in bone quality between males and females illustrates the importance of separating experimental groups by sex, genotype, and phenotype, and provides potential clinical insight as to how males and females alveolar bone may respond differently to loads than the long bones. The OTM protocol in mice will continue to assist in scientific research to help us learn how to optimize orthodontic treatment and develop innovations in the field.