Impact of Leptin on Periodontal Ligament Fibroblasts during Mechanical Strain.

Agnes Schröder,Anna Damanaki,Peter Proff,Gerrit Spanier,Eva Paddenberg,Andrea Meyer,Christian Kirschneck

doi:10.3390/ijms22136847

Abstract

Orthodontic treatment to correct dental malocclusions leads to the formation of pressure zones in the periodontal ligament resulting in a sterile inflammatory reaction, which is mediated by periodontal ligament fibroblasts (PDLF). Leptin levels are elevated in obesity and chronic inflammatory responses. In view of the increasing number of orthodontic patients with these conditions, insights into effects on orthodontic treatment are of distinct clinical relevance. A possible influence of leptin on the expression profile of PDLF during simulated orthodontic mechanical strain, however, has not yet been investigated. In this study, PDLF were exposed to mechanical strain with or without different leptin concentrations. The gene and protein expression of proinflammatory and bone-remodelling factors were analysed with RT-qPCR, Western-blot and ELISA. The functional analysis of PDLF-induced osteoclastogenesis was analysed by TRAP (tartrate-resistant acid phosphatase) staining in coculture with human macrophages. Pressure-induced increase of proinflammatory factors was additionally elevated with leptin treatment. PDLF significantly increased RANKL (receptor activator of NF-kB ligand) expression after compression, while osteoprotegerin was downregulated. An additional leptin effect was demonstrated for RANKL as well as for subsequent osteoclastogenesis in coculture after TRAP staining. Our results suggest that increased leptin concentrations, as present in obese patients, may influence orthodontic tooth movement. In particular, the increased expression of proinflammatory factors and RANKL as well as increased osteoclastogenesis can be assumed to accelerate bone resorption and thus the velocity of orthodontic tooth movement in the orthodontic treatment of obese patients.

Highlights

The exact mechanisms of orthodontic tooth movement to therapeutically correct misaligned teeth and malocclusions with all their complex interrelationships have been studied for over 100 years [1] and are still an integral part of current research
We checked whether leptin receptors (LEP-R) were expressed in periodontal ligament fibroblasts (PDLF) and if this expression was affected by compressive strain
To determine the optimal leptin concentrations for the following experiments, we tested different concentrations ranging from leptin levels detectable in gingival fluid [32] and concentrations already reported to be effective for experiments with gingival fibroblasts and PDLF [33]

Summary

Introduction

The exact mechanisms of orthodontic tooth movement to therapeutically correct misaligned teeth and malocclusions with all their complex interrelationships have been studied for over 100 years [1] and are still an integral part of current research. Apart from macrophages [2], T cells [3] and other cell populations, periodontal ligament fibroblasts (PDLF) comprise the major cell populations of the periodontal ligament and are subjected to compressive and tensile mechanical strain during orthodontic treatment [4]. These cells are responsible for the formation of collagen fibres, the regulation of tissue homeostasis and the activation of the non-specific immune system [5]. Through an autocrine feedback mechanism of PDLF, the expression of proinflammatory cytokines, such as interleukin-1 (IL1), interleukin-6

Methods

Results

Conclusion