Title: The Effect of High Bone Mass on Orthodontic Tooth Movement
Robert Holland (Presenter)
Indiana University School of Dentistry
Carol Bain, Indiana University School of Dentistry
Rawan Alrasheed, IUPUI
Alexander Robling, Indiana Univeristy School of Medicine Department of Anatomy and Cell Biology
Achint Utreja, Indiana University
Objectives: Low-density lipoprotein receptor-related protein 5 (Lrp5) is a co-receptor of the Wnt cell signaling pathway, that is a crucial regulator of bone homeostasis. Overexpression of Lrp5 leads to a high bone mass (HBM) phenotype in mice. As orthodontic tooth movement (OTM) results from altered bone remodeling due to the application of mechanical force, the objective of this study was to analyze the effect of Lrp5 overexpression on OTM in an animal model.
Methods: Thirty two Lrp5 overexpressing mice (n=16/group A214V and G171V HBM mice) and sixteen C57BL/6 wildtype (WT) mice were included in the study. The maxillary first molar on the experimental side was tipped mesially by applying orthodontic force with a closed-coil NiTi spring for 3 weeks. Following OTM, the dissected tissues were scanned for micro-CT analysis and processed for histology. Immunostaining for Lrp5 and sclerostin (Sost), and TRAP staining for osteoclasts were performed and a region of interest (ROI) was defined in the furcation area of the maxillary first molar for quantification.
Results: Micro-CT analysis showed a significant decrease in tooth movement in the Lrp5-HBM mice compared to the wildtype group, with the least movement observed in the A214V group. Both HBM groups had higher percent bone volume (BV/TV), lower bone surface/volume ratio (BS/BV) and increased trabecular thickness (Tb.Th) compared to the WT group. Histological analysis showed increased Lrp5 imunnostaining in the PDL in both HBM groups compared to the WT group. Sclerostin expression was decreased in the A214V group. Osteocyte cell density and osteoclast activity in the ROI were decreased in both HBM groups compared to WT animals.
Conclusions: Overexpression of Lrp5 decreases the rate of OTM in an animal model. Understanding the Wnt signaling pathway components involved in OTM can lead to more predictable treatment outcomes in the future.