A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement.

Sinan Şen,Ralf Erber,Christopher J Lux

doi:10.3390/ijms22158297

Sinan Şen, Ralf Erber + Show 1 more

Open Access

https://doi.org/10.3390/ijms22158297

Copy DOI

Abstract

Background: Induced tooth movement during orthodontic therapy requires mechano-induced bone remodeling. Besides various cytokines and growth-factors, neuronal guidance molecules gained attention for their roles in bone homeostasis and thus, potential roles during tooth movement. Several neuronal guidance molecules have been implicated in the regulation of bone remodeling. Amongst them, Semaphorin 3A is particular interesting as it concurrently induces osteoblast differentiation and disturbs osteoclast differentiation. Methods: Mechano-regulation of Sema3A and its receptors PlexinA1 and Neuropilin (RT-qPCR, WB) was evaluated by applying compressive and tension forces to primary human periodontal fibroblasts (hPDLF) and alveolar bone osteoblasts (hOB). The association of the transcription factor Osterix (SP7) and SEMA3A was studied by RT-qPCR. Mechanisms involved in SEMA3A-mediated osteoblast differentiation were assessed by Rac1GTPase pull-downs, β-catenin expression analyses (RT-qPCR) and nuclear translocation assays (IF). Osteogenic markers were analyzed by RT-qPCR. Results: SEMA3A, PLXNA1 and NRP1 were differentially regulated by tension or compressive forces in hPDLF. Osterix (SP7) displayed the same pattern of regulation. Recombinant Sema3A induced the activation of Rac1GTPase, the nuclear translocation of β-catenin and the expression of osteogenic marker genes. Conclusion: Sema3A, its receptors and Osterix are regulated by mechanical forces in hPDLF. SEMA3A upregulation was associated with Osterix (SP7) modulation. Sema3A-enhanced osteogenic marker gene expression in hOB might be dependent on a pathway involving Rac1GTPase and β-catenin. Thus, Semaphorin 3A might contribute to bone remodeling during induced tooth movement.

Highlights

Tooth and jaw misalignments with treatment needs occur with a high prevalence [1,2]
A decisive prerequisite indicating the participation of Semaphorin 3a in the control of bone remodeling during orthodontic tooth movement would be its modulation by mechanical forces in the cells of the periodontium
Our results for osteoblasts of the alveolar bone correspond to the current state of research, which increasingly accepts an important function of Semaphorin 3A (Sema3A)-dependent signaling for dental hard tissue formation and bone remodeling in the periodontium and in vitro [43,44]

Summary

Introduction

Tooth and jaw misalignments with treatment needs occur with a high prevalence [1,2]. generally well tolerated, there are side effects during orthodontic therapy with fixed appliances. By far the most serious side effect is the possibility of the development of orthodontically induced root resorptions (OIRR) [4] Such root resorptions are likely closely linked to resorptive events of the bone during orthodontic tooth movement, at the molecular level [5,6]. Induced tooth movement during orthodontic therapy requires mechanoinduced bone remodeling. Methods: Mechano-regulation of Sema3A and its receptors PlexinA1 and Neuropilin (RT-qPCR, WB) was evaluated by applying compressive and tension forces to primary human periodontal fibroblasts (hPDLF) and alveolar bone osteoblasts (hOB). Recombinant Sema3A induced the activation of Rac1GTPase, the nuclear translocation of β-catenin and the expression of osteogenic marker genes. Sema3A-enhanced osteogenic marker gene expression in hOB might be dependent on a pathway involving Rac1GTPase and β-catenin. Semaphorin 3A might contribute to bone remodeling during induced tooth movement

Objectives

Methods

Results

Discussion

Conclusion