Amino Acids

, Volume 47, Issue 11, pp 2447–2455 | Cite as

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

  • Giovanni Matarese
  • Monica Currò
  • Gaetano Isola
  • Daniela Caccamo
  • Mercurio Vecchio
  • Maria Laura Giunta
  • Luca Ramaglia
  • Giancarlo Cordasco
  • Ray C. Williams
  • Riccardo Ientile
Original Article


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.


RANKL/OPG Chronic periodontitis Transglutaminase Monocytes/macrophages Inflammation Human periodontal fibroblasts 



Alkaline phosphatase




Chronic periodontitis


Fetal bovine serum




Human periodontal ligament


High mobility group box 1






Nuclear factor-kappa B


Receptor activator of nuclear factor-kappa B ligand




Periodontal ligament


Tumor necrosis factor-α


Tissue-type transglutaminase




Conflict of interest

This work has been performed with Departmental funding only. The authors declare that they have no conflict of interest to declare.


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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Giovanni Matarese
    • 1
  • Monica Currò
    • 2
  • Gaetano Isola
    • 1
    • 3
  • Daniela Caccamo
    • 2
  • Mercurio Vecchio
    • 2
  • Maria Laura Giunta
    • 2
  • Luca Ramaglia
    • 3
  • Giancarlo Cordasco
    • 1
  • Ray C. Williams
    • 4
  • Riccardo Ientile
    • 2
  1. 1.Department of Specialist Medical-Surgical Experimental Sciences and OdontostomatologyUniversity of MessinaMessinaItaly
  2. 2.Department of Biomedical Sciences and Morpho-Functional ImagingUniversity of Messina, Polyclinic Hospital UniversityMessinaItaly
  3. 3.Department of Neurosciences, Reproductive and Odontostomatological SciencesSchool of Medicine University “Federico II”NaplesItaly
  4. 4.Dean, School of Dental MedicineStony Brook UniversityStony BrookUSA

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