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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Alvarez, M. M. P. [1] ; Moura, G. E. [1] ; Machado, M. F. M. [2] ; Viana, G. M. [1] ; de Souza Costa, C. A. [3] ; Tjaderhane, L. [4, 5, 6, 7, 8] ; Nader, H. B. [1] ; Tersariol, I. L. S. [1] ; Nascimento, F. D. [2]
Total Authors: 9
[1] Fed Univ Sao Paulo UNIFESP, Dept Biochem, Mol Biol Div, Rua Tres Maio, 100-4th Floor, BR-04044020 Sao Paulo, SP - Brazil
[2] Univ Mogi Das Cruzes, Interdisciplinary Ctr Biochem Invest CIIB, Av Dr Candido Xavier Almeida & Souza 200 1S15, BR-08780911 Mogi Das Cruzes, SP - Brazil
[3] Univ Estadual Paulista, Univ Estadual Paulista, Araraquara Sch Dent, Dept Physiol & Pathol, Sao Paulo, SP - Brazil
[4] Oulu Univ Hosp, Med Res Ctr Oulu, Oulu - Finland
[5] Univ Oulu, Oulu - Finland
[6] Univ Helsinki, Dept Oral & Maxillofacial Dis, Helsinki - Finland
[7] Helsinki Univ Hosp, Helsinki - Finland
[8] Oulu Univ Hosp, Res Unit Oral Hlth Sci, Oulu - Finland
Total Affiliations: 8
Document type: Journal article
Source: JOURNAL OF DENTAL RESEARCH; v. 96, n. 13, p. 1518-1525, DEC 2017.
Web of Science Citations: 1

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. (AU)

FAPESP's process: 13/05822-9 - Proteinase-Activated Receptors (PARs) in the dentin-pulp complex: identification, modulation and signal tranduction in caries disease
Grantee:Fábio Dupart Nascimento
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 15/03964-6 - Glycosaminoglycans and proteoglycans: interplay between structure and function
Grantee:Helena Bonciani Nader
Support type: Research Projects - Thematic Grants