Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages
- 382 Downloads
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.
KeywordsRANKL/OPG Chronic periodontitis Transglutaminase Monocytes/macrophages Inflammation Human periodontal fibroblasts
Fetal bovine serum
Human periodontal ligament
High mobility group box 1
Nuclear factor-kappa B
Receptor activator of nuclear factor-kappa B ligand
Tumor necrosis factor-α
Conflict of interest
This work has been performed with Departmental funding only. The authors declare that they have no conflict of interest to declare.
- Bostanci N, Ilgenli T, Emingil G, Afacan B, Han B, Toz H, Berdeli A, Atilla G, McKay IJ, Hughes FJ, Belibasakis GN (2007) Differential expression of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin mRNA in periodontal diseases. J Periodontal Res 42:287–293CrossRefPubMedGoogle Scholar
- Matarese G, Isola G, Anastasi GP, Favaloro A, Milardi D, Vermiglio G, Vita G, Cordasco G, Cutroneo G (2012) Immunohistochemical analysis of TGF-β1 and VEGF in gingival and periodontal tissues: a role of these biomarkers in the pathogenesis of scleroderma and periodontal disease. Int J Mol Med 30:502–508PubMedGoogle Scholar
- Matarese G, Isola G, Anastasi GP, Cutroneo G, Cordasco G, Favaloro A, Vita G, Vermiglio G, Milardi D, Zizzari VL, Tetè S, Perillo L (2013) Effects of the transforming growth factor beta 1 and vascular endothelial growth factor expressions in the pathogenesis of periodontal disease. Eur J Inflamm 11:479–488Google Scholar
- Vardar-Sengul S, Arora S, Baylas H, Mercola D (2009) Expression profile of human gingival fibroblasts induced by interleukin-1beta reveals central role of nuclear factor-kappa B in stabilizing human gingival fibroblasts during inflammation. J Periodontol 80:833–849PubMedCentralCrossRefPubMedGoogle Scholar