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

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http://hdl.handle.net/10138/298146

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Alvarez , M M P , Moura , G E , Machado , M F M , Viana , G M , de Souza Costa , C A , Tjaderhane , L , Nader , H B , Tersariol , I L S & Nascimento , F D 2017 , ' PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells ' , Journal of Dental Research , vol. 96 , no. 13 , pp. 1518-1525 . https://doi.org/10.1177/0022034517719415

Title: PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells
Author: Alvarez, M. M. P.; Moura, G. E.; Machado, M. F. M.; Viana, G. M.; de Souza Costa, C. A.; Tjaderhane, L.; Nader, H. B.; Tersariol, I. L. S.; Nascimento, F. D.
Contributor: University of Helsinki, Clinicum
Date: 2017-12
Language: eng
Number of pages: 8
Belongs to series: Journal of Dental Research
ISSN: 0022-0345
URI: http://hdl.handle.net/10138/298146
Abstract: Protease-activated receptors (PARs) are G protein-coupled receptors, which are activated by proteolytical cleavage of the amino-terminus and act as sensors for extracellular proteases. We hypothesized that PAR-1 and PAR-2 can be modulated by inflammatory stimulus in human dental pulp cells. PAR-1 and PAR-2 gene expression in human pulp tissue and MDPC-23 cells were analyzed by quantitative polymerase chain reaction. Monoclonal PAR-1 and PAR-2 antibodies were used to investigate the cellular expression of these receptors using Western blot, flow cytometry, and confocal microscopy in MDPC-23 cells. Immunofluorescence assays of human intact and carious teeth were performed to assess the presence of PAR-1 and PAR-2 in the dentin-pulp complex. The results show for the first time that human odontoblasts and MDPC-23 cells constitutively express PAR-1 and PAR-2. PAR-2 activation increased significantly the messenger RNA expression of matrix metalloproteinase (MMP)-2, MMP-9, MMP-13, and MMP-14 in MDPC-23 cells (P <0.05), while the expression of these enzymes decreased significantly in the PAR-1 agonist group (P <0.05). The high-performance liquid chromatography and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analysis showed the presence of MMP-13 activity cleaving PAR-1 at specific, noncanonical site TLDPRS42 down arrow(FLL)-L-43 in human dental pulp tissues. Also, we detected a presence of a trypsin-like activity cleaving PAR-2 at canonical site SKGR(20)down arrow S(21)LIGRL in pulp tissues. Confocal microscopy analysis of human dentin-pulp complex showed intense positive staining of PAR-1 and PAR-2 in the odontoblast processes in dentinal tubules of carious teeth compared to intact ones. The present results support the hypothesis of activation of the upregulated PAR-1 and PAR-2 by endogenous proteases abundant during the inflammatory response in dentin-pulp complex.
Subject: proteinase-activated receptor (PAR)
dentin-pulp complex
odontoblasts
caries
proteolytic enzymes
matrix metalloproteinases
PROTEINASE-ACTIVATED RECEPTOR-2
OSTEOCLAST DIFFERENTIATION
CYSTEINE CATHEPSINS
DENTAL-PULP
INFLAMMATION
OSTEOBLASTS
PHYSIOLOGY
RESPONSES
CARIES
MMPS
313 Dentistry
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