Osteocyte regulation of orthodontic force-mediated tooth movement via RANKL expression

Ayumi Shoji-Matsunaga,Takehito Ono,Tomoki Nakashima,Mikihito Hayashi,Keiji Moriyama,Hiroshi Takayanagi

doi:10.1038/s41598-017-09326-7

Abstract

Orthodontic tooth movement is achieved by the remodeling of the alveolar bone surrounding roots of teeth. Upon the application of orthodontic force, osteoclastic bone resorption occurs on the compression side of alveolar bone, towards which the teeth are driven. However, the molecular basis for the regulatory mechanisms underlying alveolar bone remodeling has not been sufficiently elucidated. Osteoclastogenesis is regulated by receptor activator of nuclear factor-κB ligand (RANKL), which is postulated to be expressed by the cells surrounding the tooth roots. Here, we show that osteocytes are the critical source of RANKL in alveolar bone remodeling during orthodontic tooth movement. Using a newly established method for the isolation of periodontal tissue component cells from alveolar bone, we found that osteocytes expressed a much higher amount of RANKL than other cells did in periodontal tissue. The critical role of osteocyte-derived RANKL was confirmed by the reduction of orthodontic tooth movement in mice specifically lacking RANKL in osteocytes. Thus, we provide in vivo evidence for the key role of osteocyte-derived RANKL in alveolar bone remodeling, establishing a molecular basis for orthodontic force-mediated bone resorption.

Highlights

Bone is constantly being renewed by the balanced activities of osteoblastic bone formation and osteoclastic bone resorption, both of which occur at the bone surface
Previous studies have suggested that periodontal tissue component cells express RANKL and induce osteoclastgenesis[20, 21], the source of RANKL in orthodontic tooth movement has not been elucidated because of the lack the cell-specific gene deletion system
This study shows that RANKL expressed by osteocytes functions as a potent driving factor in the induction of osteoclastogenesis during orthodontic tooth movement (Supplementary Fig. 3)

Summary

Introduction

Bone is constantly being renewed by the balanced activities of osteoblastic bone formation and osteoclastic bone resorption, both of which occur at the bone surface. Osteoblasts and bone marrow stromal cells were previously thought to be the major cell types that express RANKL to support osteoclastogenesis[12, 13]. It has been clearly demonstrated using a conditional knockout system that the RANKL derived from osteocytes contributes more significantly to bone remodeling, rather than that from osteoblasts[14,15,16,17]. We show that osteocytes substantially express RANKL among the periodontal tissue component cells, and demonstrate that the osteocyte derived-RANKL regulates osteoclastogenesis during orthodontic tooth movement. This study establishes the crucial role of osteocyte RANKL-mediated osteoclastogenesis in alveolar bone remodeling, which can facilitate the development of novel therapeutic strategies in orthodontics

Methods

Results

Conclusion