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Effect of activation of Protease-Activated Receptor type 2 (PAR-2) on the osteoclastic activity in periodontal ligament cells

Grant number: 16/11399-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): December 01, 2016
Effective date (End): November 30, 2019
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal researcher:Marinella Holzhausen Caldeira
Grantee:Bruno Nunes de França
Home Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Periodontitis is defined as a chronic inflammatory disease that results in the destruction of periodontal tissue support formed by cementum, alveolar bone and periodontal ligament. Such destruction is due to the persistent presence of specific microorganisms in periodontal tissues. Studies indicate that bacterial proteases have the ability to modulate the immune-inflammatory response of the host bacterial cysteine proteases produced by Porphyromonas gingivalis, can act as signaling molecules by binding to the protease-activated receptor type 2 (PAR-2). The PAR-2 has an important role in inflammation and are associated with increased inflammatory mediators associated with the destruction of the periodontium, IL-6, IL8, TNF-±, MMP-2, MMP-8, etc. in addition it was demonstrated that the PAR-2 has a role in bone resorption by stimulating the regulation of bone remodeling factors such as MMP-1, MMP-9, IL-6 and RANKL. Still, it can act on the differentiation of osteoblasts and osteoclasts in the bone growth and repair.undifferentiated mesenchymal cells of the periodontal ligament collected teeth with primary resorption had increased expression of runt-related factor transcription 2 (RUNX2), which leads to an increase in binding levels of the receptor activator of nuclear factor kappa beta (RANKL), and reduction of osteoprotegerin (OPG). This imbalance between RANKL and OPG leads to increased osteoclast differentiation, possibly contributing to increased periodontal bone loss. There is a need for further studies to elucidate the effect of PAR-2 activation on periodontal tissues. The aim of this study is to evaluate the effect of PAR-2 activation of osteoclast activity of periodontal ligament cells. It will evaluate the effect of PAR-2 activation on the expression of Runx2, RANKL, OPG, ALP, OPN and OC, and the influence of PAR-2 on cell proliferation of the PDL addition of IL-10 production and TGF -ß1. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROVAI, EMANUEL SILVA; BATITUCCI AMBROSIO, LUCAS MACEDO; DE FRANCA, BRUNO NUNES; DE OLIVEIRA, LETICIA RODRIGUES; GASPARONI, LETICIA MIQUELITTO; SIPERT, CARLA RENATA; HOLZHAUSEN, MARINELLA. Protease-Activated Receptor Type 1 Activation Enhances Osteogenic Activity in Human Periodontal Ligament Stem Cells. STEM CELLS INTERNATIONAL, . (15/07396-2, 15/23746-3, 15/11587-8, 16/11399-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FRANÇA, Bruno Nunes de. Effect of type 2 protease activated receptor (PAR-2) activation in the osteogenic activity of the periodontal ligament stem cells. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Odontologia (FO/SDO) São Paulo.

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