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Open Access 01-12-2013 | Research

TGF-β1 sensitizes TRPV1 through Cdk5 signaling in odontoblast-like cells

Authors: Elias Utreras, Michaela Prochazkova, Anita Terse, Jacklyn Gross, Jason Keller, Michael J Iadarola, Ashok B Kulkarni

Published in: Molecular Pain | Issue 1/2013

Abstract

Background

Odontoblasts are specialized cells that form dentin and they are believed to be sensors for tooth pain. Transforming growth factor-β1 (TGF-β1), a pro-inflammatory cytokine expressed early in odontoblasts, plays an important role in the immune response during tooth inflammation and infection. TGF-β1 is also known to participate in pain signaling by regulating cyclin-dependent kinase 5 (Cdk5) in nociceptive neurons of the trigeminal and dorsal root ganglia. However, the precise role of TGF-β1 in tooth pain signaling is not well characterized. The aim of our present study was to determine whether or not in odontoblasts Cdk5 is functionally active, if it is regulated by TGF-β1, and if it affects the downstream pain receptor, transient receptor potential vanilloid-1 (TRPV1).

Results

We first determined that Cdk5 and p35 are indeed expressed in an odontoblast-enriched primary preparation from murine teeth. For the subsequent analysis, we used an odontoblast-like cell line (MDPC-23) and found that Cdk5 is functionally active in these cells and its kinase activity is upregulated during cell differentiation. We found that TGF-β1 treatment potentiated Cdk5 kinase activity in undifferentiated MDPC-23 cells. SB431542, a specific inhibitor of TGF-β1 receptor 1 (Tgfbr1), when co-administered with TGF-β1, blocked the induction of Cdk5 activity. TGF-β1 treatment also activated the ERK1/2 signaling pathway, causing an increase in early growth response-1 (Egr-1), a transcription factor that induces p35 expression. In MDPC-23 cells transfected with TRPV1, Cdk5-mediated phosphorylation of TRPV1 at threonine-407 was significantly increased after TGF-β1 treatment. In contrast, SB431542 co-treatment blocked TRPV1 phosphorylation. Moreover, TGF-β1 treatment enhanced both proton- and capsaicin-induced Ca²⁺ influx in TRPV1-expressing MDPC-23 cells, while co-treatment with either SB431542 or roscovitine blocked this effect.

Conclusions

Cdk5 and p35 are expressed in a murine odontoblast-enriched primary preparation of cells from teeth. Cdk5 is also functionally active in odontoblast-like MDPC-23 cells. TGF-β1 sensitizes TRPV1 through Cdk5 signaling in MDPC-23 cells, suggesting the direct involvement of odontoblasts and Cdk5 in dental nociceptive pain transduction.

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Title: TGF-β1 sensitizes TRPV1 through Cdk5 signaling in odontoblast-like cells
Authors: Elias Utreras
Michaela Prochazkova
Anita Terse
Jacklyn Gross
Jason Keller
Michael J Iadarola
Ashok B Kulkarni
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2013
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-9-24

Keynote webinar | Spotlight on medication adherence

Springer Medicine

TGF-β1 sensitizes TRPV1 through Cdk5 signaling in odontoblast-like cells

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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