Anti-inflammatory and antiosteoclastogenic activities of parthenolide on human periodontal ligament cells in vitro.

Xufang Zhang,Xueli Mao,Chen Fan,Yin Xiao

doi:10.1155/2014/546097

Abstract

Periodontitis is an inflammatory disease that causes osteolysis and tooth loss. It is known that the nuclear factor kappa B (NF-κB) signalling pathway plays a key role in the progression of inflammation and osteoclastogenesis in periodontitis. Parthenolide (PTL), a sesquiterpene lactone extracted from the shoots of Tanacetum parthenium, has been shown to possess anti-inflammatory properties in various diseases. In the study reported herein, we investigated the effects of PTL on the inflammatory and osteoclastogenic response of human periodontal ligament-derived cells (hPDLCs) and revealed the signalling pathways in this process. Our results showed that PTL decreased NF-κB activation, I-κB degradation, and ERK activation in hPDLCs. PTL significantly reduced the expression of inflammatory (IL-1β, IL-6, and TNF-α) and osteoclastogenic (RANKL, OPG, and M-CSF) genes in LPS-stimulated hPDLCs. In addition, PTL attenuated hPDLC-induced osteoclastogenic differentiation of macrophages (RAW264.7 cells), as well as reducing gene expression of osteoclast-related markers in RAW264.7 cells in an hPDLC-macrophage coculture model. Taken together, these results demonstrate the anti-inflammatory and antiosteoclastogenic activities of PTL in hPDLCs in vitro. These data offer fundamental evidence supporting the potential use of PTL in periodontitis treatment.

Highlights

Periodontitis is a highly prevalent condition in clinic and may lead to the destruction of alveolar bone and loss of teeth [1]
In response to LPS, resident Human periodontal ligament cells (hPDLCs) produce a range of inflammatory cytokines and matrix metalloproteinases (MMPs), including tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, Matrix Metalloproteinase- (MMP-)2, and MMP-9, which are responsible for activation of circulating immune cells and degradation of extracellular matrix [1, 4]
In the study reported we investigated the effects of PTL on NF-κB and extracellular signal-regulated kinases (ERK) signalling pathways in LPS-stimulated hPDLCs

Summary

Introduction

Periodontitis is a highly prevalent condition in clinic and may lead to the destruction of alveolar bone and loss of teeth [1]. Lipopolysaccharide (LPS), a key pathogenic component of gram-negative bacteria, has been broadly reported to participate in periodontitis progression by inducing host cells to produce a wide range of proinflammatory cytokines [1]. In response to LPS, resident hPDLCs produce a range of inflammatory cytokines and matrix metalloproteinases (MMPs), including tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, MMP-2, and MMP-9, which are responsible for activation of circulating immune cells and degradation of extracellular matrix [1, 4]. HPDLCs secrete osteoclastogenic-related cytokines, such as osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL), which are essential in regulating alveolar bone destruction [5]. It has been reported that the inflammation-regulating properties of hPDLCs are triggered through the nuclear factor kappa B (NF-κB) signalling pathway [6], indicating that NF-κB may be a potential target for improving periodontitis therapies

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