Role of c-Fos in orthodontic tooth movement: an in vivo study using transgenic mice

Maximilian G Decker,Cita Nottmeier,Thorsten Schinke,Till Koehne,Julia Luther,Jean-Pierre David,Michael Amling,Anke Baranowsky,Bärbel Kahl-Nieke

doi:10.1007/s00784-020-03503-1

Maximilian G Decker, Cita Nottmeier + Show 7 more

Open Access

https://doi.org/10.1007/s00784-020-03503-1

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Abstract

ObjectivesThe transcription factor c-Fos controls the differentiation of osteoclasts and is expressed in periodontal ligament cells after mechanical stimulation in vitro. However, it is unclear how c-Fos regulates orthodontic tooth movement (OTM) in vivo. The aim of this study was therefore to analyse OTM in transgenic mice with overexpression of c-Fos.Materials and methodsWe employed c-Fos transgenic mice (c-Fos tg) and wild-type littermates (WT) in a model of OTM induced by Nitinol tension springs that were bonded between the left first maxillary molars and the upper incisors. The unstimulated contralateral side served as an internal control. Mice were analysed by contact radiography, micro-computed tomography, decalcified histology and histochemistry.ResultsOur analysis of the unstimulated side revealed that alveolar bone and root morphology were similar between c-Fos tg and control mice. However, we observed more osteoclasts in the alveolar bone of c-Fos tg mice as tartrate-resistant acid phosphatase (TRAP)-positive cells were increased by 40%. After 12 days of OTM, c-Fos tg mice exhibited 62% increased tooth movement as compared with WT mice. Despite the faster tooth movement, c-Fos tg and WT mice displayed the same amount of root resorption. Importantly, we did not observe orthodontically induced tissue necrosis (i.e. hyalinization) in c-Fos tg mice, while this was a common finding in WT mice.ConclusionOverexpression of c-Fos accelerates tooth movement without causing more root resorption.Clinical relevanceAccelerated tooth movement must not result in more root resorption as higher tissue turnover may decrease the amount of mechanically induced tissue necrosis.

Highlights

Orthodontic tooth movement (OTM) is a prime example of mechanically induced bone remodelling
Quantification of alveolar bone loss (ABL) and palatal thickness revealed no differences between c-Fos tg and WT mice (Fig. 2b and c)
Quantification of the shortest distance between the 1st and 2nd molars revealed 62% increased tooth movement in c-Fos tg mice (Fig. 2e). These first analyses suggest that cFos overexpression increases OTM and that this acceleration cannot be explained by differences in alveolar bone architecture between c-Fos tg and WT mice

Summary

Introduction

Orthodontic tooth movement (OTM) is a prime example of mechanically induced bone remodelling. Genetically modified mice were used to study the genetic basis of tooth movement [6,7,8,9,10,11]. Whereas larger animal models are easier to handle, only mice offer the possibility to analyse the role of single genes during OTM in vivo. Mouse models are a valuable approach to decrease the gap that exists between our knowledge from in vitro studies and the small list of genes that are known to regulate OTM in vivo.

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