Assoc.Prof. Balázs István TÓTH
University of Pécs
Institute of Physiology

Program

"Role of TRP ion channels in dental pulp derived cells"

Despite being covered by enamel, the hardest tissue of our body, teeth show a marked sensitivity to external stimuli, which is often manifested under pathological, especially inflammatory conditions. The dental sensitivity is attributed to the sensory nerve endings innervating the pulp, which fills the cavity of the tooth. Beyond sensory fibers, pulp contains vessels and various additional cell types including odontoblasts, fibroblasts, and mesenchymal stem cells. If the hard tissues are penetrated by caries, bacteria can enter the pulpal cavity, initiating pulpitis. Pulpitis is associated with hyperalgesia toward mechanical and thermal stimuli. In this inflammatory hypersensitivity, alterations in the expression or the sensitivity of TRP channels in the sensory fibers can play a role. However, TRP channels are also expressed in non-neuronal cells of the dental pulp, which can also shape sensory and inflammatory processes.

We investigated thermo and mechanosensitive TRP channels in primary human dental pulp cells (hDPCs) and mechanosensitive ion channels in odontoblast-like cells (OBLCs) differentiated from hDPCs in vitro. 

In hDPC cultures, we established inflammatory conditions by applying pathogen-associated molecular patterns (PAMPs) activating pattern recognition Toll-like receptors (TLRs). Poly(I:C) (PIC), a ligand of TLR3, induced robust inflammatory responses: it stimulated the production of pro-inflammatory cytokines, induced oxidative stress, and upregulated TRPA1. In PIC-induced inflammatory conditions, TRPA1-mediated Ca2+ signals were highly potentiated. PIC-treated cells displayed increased Ca2+ responses to H2O2, which were abolished by TRPA1 antagonism. Moreover, PIC resulted in mitochondrial dysfunctions alleviated by the antioxidant glutathione and partly by TRPA1 antagonism or silencing.

We also studied the potential antiinflammatory effect of 3-O-acetyl-11-keto-β-boswellic acid (AKBA), an active ingredient in the resin of the Indian frankincense tree (Boswellia serrata). AKBA significantly reduced the production of certain inflammatory cytokines, inhibited the upregulation of TRPA1 and reduced the amplitude of Ca2+ signals mediated by this ion channel.

In OBLCs, we identified the expression of several mechanosensitive cation channels, and hypotonic stimuli induced intracellular Ca2+ signals from the extracellular space which were abolished by GsMTx4, an inhibitor of mechanosensitive Ca2+ channels. Using quantitative PCR, we identified the expression of several mechanosensitive cation channels. Applying pharmacological tools, the role of Piezo 1, TRPA1, TRPV2, and TRPV4 was supported in the mechanotransduction of the OBLCs.

Our results suggest that pulpal TRP channels are not only important players in dental sensory transduction but also promising pharmacological targets to combat pulpitis and alleviate inflammation-related pulpal tissue damage.

Host: Gabor Tajti

Contact for questions: Helmut KUBISTA