The role of inhibition of osteocyte apoptosis in mediating orthodontic tooth movement and periodontal remodeling: a pilot study

Michele Kaplan; Zana Kalajzic; Thomas Choi; Imad Maleeh; Christopher L Ricupero; Michelle N Skelton; Madeleine L Daily; Jing Chen; Sunil Wadhwa

doi:10.1186/s40510-021-00366-4

The role of inhibition of osteocyte apoptosis in mediating orthodontic tooth movement and periodontal remodeling: a pilot study

Prog Orthod. 2021 Jul 26;22(1):21. doi: 10.1186/s40510-021-00366-4.

Authors

Michele Kaplan¹, Zana Kalajzic², Thomas Choi³, Imad Maleeh³, Christopher L Ricupero³, Michelle N Skelton³, Madeleine L Daily³, Jing Chen³, Sunil Wadhwa³

Affiliations

¹ Division of Orthodontics, College of Dental Medicine, Columbia University, New York, NY, USA. michelekaplan22@gmail.com.
² Department of Oral Health and Diagnostic Sciences, Division of Oral Medicine, UConn Health, Farmington, CT, USA.
³ Division of Orthodontics, College of Dental Medicine, Columbia University, New York, NY, USA.

Abstract

Background: Orthodontic tooth movement (OTM) has been shown to induce osteocyte apoptosis in alveolar bone shortly after force application. However, how osteocyte apoptosis affects orthodontic tooth movement is unknown. The goal of this study was to assess the effect of inhibition of osteocyte apoptosis on osteoclastogenesis, changes in the alveolar bone density, and the magnitude of OTM using a bisphosphonate analog (IG9402), a drug that affects osteocyte and osteoblast apoptosis but does not affect osteoclasts.

Material and methods: Two sets of experiments were performed. Experiment 1 was used to specifically evaluate the effect of IG9402 on osteocyte apoptosis in the alveolar bone during 24 h of OTM. For this experiment, twelve mice were divided into two groups: group 1, saline administration + OTM_24-h (n=6), and group 2, IG9402 administration + OTM_24-h (n=6). The contralateral unloaded sides served as the control. The goal of experiment 2 was to evaluate the role of osteocyte apoptosis on OTM magnitude and osteoclastogenesis 10 days after OTM. Twenty mice were divided into 4 groups: group 1, saline administration without OTM (n=5); group 2, IG9402 administration without OTM (n=5); group 3, saline + OTM_10-day (n=6); and group 4, IG9402 + OTM_10-day (n=4). For both experiments, tooth movement was achieved using Ultra Light (25g) Sentalloy Closed Coil Springs attached between the first maxillary molar and the central incisor. Linear measurements of tooth movement and alveolar bone density (BVF) were assessed by MicroCT analysis. Cell death (or apoptosis) was assessed by terminal dUTP nick-end labeling (TUNEL) assay, while osteoclast and macrophage formation were assessed by tartrate-resistant acid phosphatase (TRAP) staining and F4/80+ immunostaining.

Results: We found that IG9402 significantly blocked osteocyte apoptosis in alveolar bone (AB) at 24 h of OTM. At 10 days, IG9402 prevented OTM-induced loss of alveolar bone density and changed the morphology and quality of osteoclasts and macrophages, but did not significantly affect the amount of tooth movement.

Conclusion: Our study demonstrates that osteocyte apoptosis may play a significant role in osteoclast and macrophage formation during OTM, but does not seem to play a role in the magnitude of orthodontic tooth movement.

Keywords: Bisphosphonate; Orthodontic tooth movement; Osteocyte apoptosis.

MeSH terms

Animals
Apoptosis
Bone Remodeling
Mice
Osteocytes*
Pilot Projects
Tooth Movement Techniques*