The Possible Role of Neutrophils in the Induction of Osteoclastogenesis.

Carolyn G J Moonen,Elena A Nicu,Patrice E Poubelle,Bruno G Loos,Patrick Rijkschroeff,Teun J De Vries

doi:10.1155/2019/8672604

Abstract

The ligand of the receptor activator of NF-κB (RANKL) is a key molecule in the formation of osteoclasts, the key cells that cause the disease-associated alveolar bone resorption in periodontitis. We hypothesized that polymorphonuclear leukocytes (PMNs), found as the most prominent cells of inflamed periodontal tissues, could play an important role in providing signals to trigger osteoclastogenesis and thus activating pathological bone resorption in periodontitis. RANKL expression was investigated on circulatory PMNs (cPMNs) and oral PMNs (oPMNs) taken from both controls and periodontitis patients. On average, 2.3% and 2.4% RANKL expression was detected on the cPMNs and oPMNs from periodontitis patients, which did not differ significantly from healthy controls. Since cPMNs may acquire a more osteoclastogenesis-facilitating phenotype while migrating into the inflamed periodontium, we next investigated whether stimulated (with LPS, TNF-α, or IL-6) cPMNs have the capacity to contribute to osteoclastogenesis. Enduring surface expression of RANKL for short-lived cells as cPMNs was achieved by fixating stimulated cPMNs. RANKL expression on stimulated cPMNs, as assessed by flow cytometry and immunohistochemistry, was limited (6.48 ± 0.72%, mean expression ± SEM) after 24 and 48 hours of stimulation with LPS. Likewise, stimulation with TNF-α and IL-6 resulted in limited RANKL expression levels. These limited levels of expression did not induce osteoclastogenesis when cocultured with preosteoclasts for 10 days. We report that, under the aforementioned experimental conditions, neither cPMNs nor oPMNs directly induced osteoclastogenesis. Further elucidation of the key cellular players and immune mediators that stimulate alveolar bone resorption in periodontitis will help to unravel its pathogenesis.

Highlights

Periodontitis is a chronic inflammatory disease of the toothsupporting tissues
In part A, we investigated whether oral PMNs (oPMNs), as a model representing the activated polymorphonuclear leukocytes (PMNs) from periodontitis lesions, express recognize activator NF-kappa B-ligand (RANKL) and whether they can be primed and activated in response to the continuous presence of extracellular stimulants that are present in the gingival sulcus and oral cavity
In part B of this study, we investigated whether circulatory PMNs (cPMNs), after activation by the immunological modulators LPS, IL-6, or TNF-α, have the capacity to contribute to osteoclast formation via RANKL expression as previously published by Chakravarti et al [37]

Summary

Introduction

Periodontitis is a chronic inflammatory disease of the toothsupporting tissues (e.g., the periodontium). The chronic inflammatory cell infiltration of the periodontal soft tissues is accompanied by osteoclast-induced alveolar bone resorption, the hallmark of periodontitis progression [1, 2]. Osteoclasts are derived from monocyte/macrophage precursors and regulate bone resorption. Monocyte differentiation into osteoclasts requires the activation of their RANK receptors that recognize activator NF-kappa B-ligand (RANKL) [3]. Expression of RANKL has been reported on a wide variety of cells of the periodontium, including T cells, B cells [6], and periodontal ligament and gingival fibroblasts [7]. Alveolar bone osteocytes express RANKL, and it has recently been demonstrated that especially osteocyteexpressed RANKL could be crucial in the initiation of periodontitis as demonstrated in a RANKL knock-out mouse

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