Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages

Abstract

Recent evidence emphasized that transglutaminase 2 (TG2), a protein cross-linking enzyme, may play a role in the early phase of inflammation. High levels of TG2 have been associated with the constitutive activation of nuclear factor-kappa B (NF-κB) that is considered the main regulator of inflammation. In this context, the receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-κB have extensive functions in the regulation of cytokine secretion associated with different pathological conditions. The human periodontal ligament (HPDL) cells, which express and secrete osteoprotegerin (OPG) and RANKL, represent an useful "ex vivo" model for monitoring cell response in inflammatory microenvironments, such as periodontitis-dependent tissue response. Thus, we evaluated TG2 expression and alterations in RANKL/OPG ratio occurring in cultured HPDL cells. The HPDL cells were obtained from patients with chronic periodontitis (CP) and healthy subjects. We observed the up-regulation of some inflammatory markers, such as IL-6, TNF-α, and HMGB-1, and at the same time an increase in TG2 mRNA levels in HPDL cells from CP patients compared with healthy subjects. We found a positive correlation between RANKL/OPG ratio and TG2 mRNA levels in HPDL cells from CP patients. In the parallel experiments, we demonstrated that TG2 inhibition reduced RANKL expression in both HPDL cells from CP patients and monocytes differentiated to macrophages by tetradecanoyl phorbol acetate treatment. Given the RANKL key role in NF-κB pathway and the observed up-regulation of pro-inflammatory cytokines, our data suggest that TG2 may be involved in molecular mechanisms of inflammatory response occurring in periodontal disease.

Letter to the Editor: Re: Increased Periodontal Attachment Loss in Patients With Systemic Sclerosis

“…Periodontal disease, 3 as well as widening of periodontal ligament spaces and abnormalities in periodontal microcirculation, have been reported as a frequent finding as part of the global fibrosing aspects of SSc. 4 Recently, in accord with the authors' results, we reported a detectable prevalence of symptoms and signs of dysfunction of TMJs and self-reported symptoms in SSc patients (limited and diffuse) compared with healthy subjects. 5 Notably, our study primarily demonstrated in the SSc group an association between TMJ symptoms with MRSS and the mean duration of SSc.…”

“…SSc is a multisystem disorder of the connective tissue of the skin and underlying tissues that can have significant adverse effects on the health of the mouth. Periodontal disease, 3 as well as widening of periodontal ligament spaces and abnormalities in periodontal microcirculation, have been reported as a frequent finding as part of the global fibrosing aspects of SSc 4 …”

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

“…Etiologically, inflammatory cytokines including matrix metalloproteinases (MMPs), IL-1β, IL-6, TNF-α, nitric oxide, and prostaglandin E2 seem to be involved in the process of IVDD leading to loss of cells and ECM [11,12]. Among these inflammatory cytokines, TNF-α is known as a pro-inflammatory cytokine for NPCs.…”

Gingival Crevicular Fluid and Plasma Levels of Transglutaminase‐2 and Oxidative Stress Markers in Cyclosporin A‐Induced Gingival Overgrowth

“…In addition to causing increased matrix deposition through activation of TGF‐β1, TGM‐2 cross‐linking of ECM results in reduction in matrix turnover leading to net deposition and accumulation 45 , 46 . Cytokines and growth factors secreted during early phases of cell injury regulate TGM‐2 expression 47 that has been shown to play a relevant role in inflammatory states 47 , 48 . In the present study, both GCF and plasma levels of TGM‐2 were elevated in CsA GO+ group compared with G and H groups.…”