ABSTRACT
OBJECTIVE: To analyse the effect of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (Lrp5) on orthodontic tooth movement (OTM). SETTING AND SAMPLE POPULATION: A split-mouth study design was utilized. Thirty-two male Lrp5-high bone mass (HBM) knock-in mice including A214V and G171V mutants (n = 16/group) and sixteen C57BL/6 wild-type (WT) mice were included in the study. MATERIALS AND METHODS: A mouse model of OTM was used for mesial movement of the maxillary first molar using a closed-coil nickel titanium (NiTi) spring attached between the molar and the incisors. After 21 days, the dissected maxillae were scanned for micro-computed tomography (micro-CT) analyses and embedded in methyl methacrylate and paraffin for histological staining and imaging. Histological analyses included immunohistochemistry for sclerostin (Sost), tartrate-resistant acid phosphatase (TRAP) staining for osteoclasts and fluorescent imaging. RESULTS: OTM in the A214V and G171V groups was significantly less than the WT group. Bone volume (BV), per cent bone volume (BV/TV) and trabecular thickness (Tb.Th) were significantly increased in both A241V and G171V animals compared to the WT animals. On the compression side, decreased osteoclast activity was seen in both A214V and G171V groups compared to the WT group. Fluorescent labelling demonstrated that the pattern of bone deposition in the A214V animals was periosteal whereas the G171V animals added bone endocortically. CONCLUSION: Gain-of-function mutations of Lrp5 decrease orthodontic tooth movement by increasing alveolar bone mass and reducing osteoclast-mediated bone resorption.