Abstract

BackgroundThe endocannabinoid system is involved in the regulation of periodontal tissue homeostasis. Synthetic cannabinoid methanandamide (Meth-AEA) has improved stability and affinity to cannabinoid receptors compared to its endogenous analog anandamide. In the present study, we investigated the effect of methanandamide on the production of pro-inflammatory mediators in primary human periodontal ligament cells (hPdLCs).MethodshPdLCs were treated with Meth-AEA for 24 h, and the resulting production of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1 was measured in the absence or the presence of Porphyromonas gingivalis lipopolysaccharide (LPS). Additionally, the effect of Meth-AEA on the proliferation/viability of hPdLCs was measured by the MTT method.ResultsMethanandamide at a concentration of 10 μM significantly inhibited P. gingivalis LPS induced production of IL-6, IL-8, and MCP-1. Basal production of IL-6 and IL-8 was slightly enhanced by 10 μM Meth-AEA. No effect of Meth-AEA on the basal production of MCP-1 was observed. Meth-AEA in concentrations up to 10 μM did not affect the proliferation/viability of hPdLCs, but significantly inhibited it at a concentration of 30 μM.ConclusionOur study suggests that the inflammatory response in periodontal ligament cells could be influenced by the activation of the cannabinoid system, which might be potentially involved in the progression of periodontal disease.

Highlights

  • The endocannabinoid system is involved in the regulation of periodontal tissue homeostasis

  • Effect of meth-are the anandamide (AEA) on the gene expression of IL-6, IL-8, and monocyte chemotactic protein (MCP)-1 in human periodontal ligament cells (hPdLCs) Figure 2 shows the effect of Meth-AEA (0.1–10 μM) on the gene expression levels of IL-6, IL-8, and MCP-1

  • We investigated for the first time the effect of Meth-AEA on the proliferation/viability and inflammatory response in primary hPdLCs in order to further clarify the potential role of the EC system in periodontitis. hPdLCs play an essential role in the maintenance of periodontal tissue homeostasis and possess the immunomodulatory properties [32, 33]

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Summary

Introduction

The endocannabinoid system is involved in the regulation of periodontal tissue homeostasis. Synthetic cannabinoid methanandamide (Meth-AEA) has improved stability and affinity to cannabinoid receptors compared to its endogenous analog anandamide. We investigated the effect of methanandamide on the production of pro-inflammatory mediators in primary human periodontal ligament cells (hPdLCs). Periodontitis is a biofilm-induced chronic inflammatory disease, which affects teeth supporting structures, including the gingival tissue, periodontal ligament, and alveolar bone [1]. The endocannabinoid (EC) system consists of endocannabinoids and cannabinoid receptor proteins. Endocannabinoids are a family of endogenous lipid neurotransmitter which activates cannabinoid receptors. Cannabinoid receptors belong to a transmembrane G-protein coupled receptor family. The primary endocannabinoid receptors cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) are expressed in various cells and tissues and in dental tissues [11]. The EC system is thought to regulate several brain processes; actual studies suggest its involvement in the regulation of bone physiology and immune response [12, 13]

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