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Protease-activated receptor type 1 (PAR1) increases CEMP1 gene expression through MAPK/ERK pathway

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Author(s):
Rovai, Emanuel Silva ; Alves, Tomaz ; Gasparoni, Leticia Miquelitto ; de Franca, Bruno Nunes ; Sipert, Carla Renata ; Kantarci, Alpdogan ; Holzhausen, Marinella
Total Authors: 7
Document type: Journal article
Source: BRAZILIAN ORAL RESEARCH; v. 36, p. 8-pg., 2022-01-01.
Abstract

PAR1 is a G-coupled protein receptor that regulates several cellular metabolism processes, including differentiation and proliferation of osteogenic and cementogenic related cells and our group previously demonstrated the regenerative potential of PAR1 in human periodontal ligament stem cells (hPDLSCs). In this study, we hypothesized that PAR1 regulates the cementogenic differentiation of hPDLSCs. Our goal was to identify the intracellular signaling pathway underlying PAR1 activation in hPDSLC differentiation. hPDLSCs were isolated using the explant technique. Cells were cultured in an osteogenic medium (OST) (alpha-MEM, 15% fetal bovine serum, L-glutamine, penicillin, streptomycin, amphotericin B, dexamethasone, and beta-glycerophosphate). The hPDLSCs were treated with a specific activator of PAR1 (PAR1 agonist) and blockers of the MAPK/ERK and PI3K pathways for 2 and 7 days. The gene expression of CEMP1 was assessed by RT-qPCR. The activation of PAR1 by its agonist peptide led to an increase in CEMP1 gene expression when compared with OST control. MAPK/ERK blockage abrogated the upregulation of CEMP1 gene expression induced by PAR1 agonist (p < 0.05). PI3K blockage did not affect the gene expression of CEMP1 at any experimental time (p > 0.05). We concluded that CEMP1 gene expression increased by PAR1 activation is MAPK/ERK- dependent and PI3K independent, suggesting that PAR1 may regulate cementogenetic differentiation of hPDLSCs. (AU)

FAPESP's process: 17/23158-0 - EFFECT OF PROTEASE ACTIVATED RECEPTOR 1 (PAR1) ACTIVATION ON THE OSTEOGENIC ACTIVITY OF MEMBRANES OF HUMAN PERIODONTAL LIGAMENT MESENCHYMAL STEM CELLS
Grantee:Marinella Holzhausen Caldeira
Support Opportunities: Regular Research Grants
FAPESP's process: 18/13818-5 - Effect of protease-activated receptor type 1 (PAR1) activation on the osteogenic activity in human periodontal ligament stem cells membranes: an in vivo study
Grantee:Tomaz Alves da Silva Neto
Support Opportunities: Scholarships in Brazil - Master