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PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells.

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  • 11 Department of Biochemistry, Molecular Biology Division, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.

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Summary

Protease-activated receptors (PARs) are expressed in human dental pulp cells and are modulated by inflammation. PAR-2 activation increases matrix metalloproteinase expression, while PAR-1 activation decreases it, suggesting a role in dental pulp inflammatory responses.

Keywords:
cariesdentin-pulp complexmatrix metalloproteinasesodontoblastsproteinase-activated receptor (PAR)proteolytic enzymes

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Dental Research

Background:

  • Protease-activated receptors (PARs) are G protein-coupled receptors that sense extracellular proteases.
  • PARs are implicated in various physiological and pathological processes, including inflammation.
  • The role of PAR-1 and PAR-2 in human dental pulp cells and their response to inflammatory stimuli is not fully understood.

Purpose of the Study:

  • To investigate the expression and function of PAR-1 and PAR-2 in human dental pulp cells.
  • To determine the effect of PAR-1 and PAR-2 activation on matrix metalloproteinase (MMP) expression in dental pulp cells.
  • To explore the presence and activation of PAR-1 and PAR-2 in the human dentin-pulp complex during carious processes.

Main Methods:

  • Quantitative polymerase chain reaction (qPCR) for gene expression analysis.
  • Western blot, flow cytometry, and confocal microscopy for protein expression and localization.
  • Immunofluorescence assays on human teeth.
  • High-performance liquid chromatography (HPLC) and mass spectrometry (MS) for protease activity analysis.

Main Results:

  • Human odontoblasts and MDPC-23 cells constitutively express PAR-1 and PAR-2.
  • PAR-2 activation significantly upregulated MMP-2, MMP-9, MMP-13, and MMP-14 mRNA expression in MDPC-23 cells.
  • PAR-1 activation significantly downregulated the expression of these MMPs.
  • MMP-13 and trypsin-like activities cleaving PAR-1 and PAR-2, respectively, were detected in human dental pulp tissues.
  • PAR-1 and PAR-2 were intensely stained in odontoblast processes within dentinal tubules of carious teeth.

Conclusions:

  • Human dental pulp cells express PAR-1 and PAR-2, which are modulated by inflammatory stimuli.
  • Differential regulation of MMPs by PAR-1 and PAR-2 suggests distinct roles in dental pulp homeostasis and pathology.
  • Upregulated PAR-1 and PAR-2 are likely activated by endogenous proteases during inflammation in the dentin-pulp complex, contributing to carious lesion progression.