Osteocyte-Intrinsic TGFβ Regulation of Alveolar Bone Remodeling Under Orthodontic Forces

Objectives: In this study, we utilize an orthodontic tooth movement (OTM) mouse model to investigate the role of osteocyte-intrinsic TGFβ signaling in alveolar bone remodeling.
Methods: 40 mice were divided equally into four groups: (1) Dmp1-Cre^-/-;TbRII^fl/fl (Control) no OTM, (2) Dmp1-Cre^+/-;TbRII^fl/fl (KO) no OTM, (3) Control OTM, and (4) KO OTM. All mice were anesthetized by intraperitoneal injection of ketamine (87mg/kg) and xylazine (13mg/kg). Next, OTM groups underwent appliance placement. The OTM appliances comprised a coiled spring ligated and bonded to the maxillary left first molar and the maxillary incisors, delivering 3-5 g of force. OTM continued for 14 days. All mice were then euthanized for ex-vivo Micro-CT scanning. Micro-CT analysis included measurement of OTM distance (mm), bone mineral density (BMD, g/cm³), and bone-to-tissue volume ratio (BV/TV, %).
Results: Firstly, the KO OTM group had significantly higher OTM distance than the Control OTM group (215.26mm and 148.34mm, respectively, p=0.0082). [AT1] [BZ2] No statistical differences in BV/TV or BMD between Control and KO mice in the no OTM groups indicated a similar alveolar bone baseline without OTM treatment. On the contrary, the KO OTM group, relative to the Control OTM group, showed lower BV/TV (48.32% and 60.64%, respectively, p=0.0463) and lower BMD (1.308g/cm³ and 1.518g/cm³, respectively, p=0.0239). Furthermore, KO OTM mice had lower BV/TV (48.32% and 72.36%, respectively, p=0.0054) than the KO no OTM mice.
Conclusions: Impaired osteocytic TGFβ signaling led to more OTM, suggesting that defective osteocyte-intrinsic TGFβ signaling dysregulates alveolar bone remodeling upon force appliance. This study furthers our understanding of the role osteocytes may play in the process of bone remodeling during OTM.