Periodontal disease influences osteoclastogenic bone markers in subjects with and without rheumatoid arthritis.

Jeneen Panezai,Per-Erik Engström,Mohammad Altamash,Ambereen Ghaffar,Anders Larsson

doi:10.1371/journal.pone.0197235

Abstract

BackgroundPeriodontal disease (PD) and rheumatoid arthritis (RA) are bone pathologies mediated through immuno-inflammatory mechanisms. The aim of this study was to investigate the serum markers osteopontin (OPN), tumor necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) receptor activator of nuclear factor‐kappa B ligand (RANKL) and RANKL/ osteoprotegerin (OPG) ratio and compare them in PD and RA groups.Materials & methodsRA (with PD = 19 and without PD = 19), PD (n = 38) and 14 healthy subjects underwent bleeding on probing (BOP) and probing pocket depth (PPD) measurement. PD was defined as PPD measuring ≥5mm registered in ≥3 sites. Marginal bone loss (MBL) for premolars and molars was measured on digital panoramic radiographs. Serum samples were collected from all subjects. OPN, TNFR1, TNFR2 and RANKL were measured by enzyme-linked immunosorbent assays (ELISAs). OPG was measured as part of a multiplex proximity extension assay (PEA).ResultsOPN, TNFR1, TNFR2 and RANKL serum levels were the highest in the RA group with PD, while the RA group without PD were comparable to PD subjects only. The RANKL/OPG ratios were comparable between PD group and both RA groups with (p = 0.051) and without PD (p = 0.37). Serum RANKL levels were associated with MBL (p = 0.008) and PPD ≥ 5mm (p = 0.01).ConclusionPeripheral osteoclastogenesis is a feature of periodontal disease with systemic levels of osteoclastogenic markers comparable to the effects observed in rheumatoid arthritis.

Highlights

Interaction between the skeletal and immune systems in health is tightly regulated to maintain normal bone homeostasis
OPN, tumor necrosis factor receptors 1 (TNFR1), TNFR2 and receptor activator of nuclear factor-kappa B ligand (RANKL) serum levels were the highest in the rheumatoid arthritis (RA) group with Periodontal disease (PD), while the RA group without PD were comparable to PD subjects only
The RANKL/OPG ratios were comparable between PD group and both RA groups with (p = 0.051) and without PD (p = 0.37)

Summary

Introduction

Interaction between the skeletal and immune systems in health is tightly regulated to maintain normal bone homeostasis. Osseous tissue turnover comprises of an episode of bone resorption followed by new bone formation This process is referred to as coupling [2]. OPN functions as a Th1 cytokine, promoting cell-mediated immune responses, and plays a role in chronic inflammatory and autoimmune diseases [4]. The proliferation of osteoblasts and the differentiation of osteoblast precursors, such as periodontal ligament cells, are significantly inhibited by TNF [6] Another member of the TNF family, receptor activator of nuclear factor “kappalight-chain-enhancer” of the activated B cells ligand (RANKL) is necessary for the formation, differentiation and activity of osteoclasts. Osteoprotegerin (OPG), along with its ligand RANKL, has been identified to play a role in the regulation of bone metabolism by mediating the signaling between osteoblast and osteoclast [15]. The aim of this study was to investigate the serum markers osteopontin (OPN), tumor necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) receptor activator of nuclear factor-kappa B ligand (RANKL) and RANKL/ osteoprotegerin (OPG) ratio and compare them in PD and RA groups

Objectives

Methods

Results

Conclusion