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Kinetics of osteoclast co-stimulatory molecules throughout experimental periodontitis and mice and its modulation by cytokines

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Author(s):
Carlos Eduardo Palanch Repeke
Total Authors: 1
Document type: Doctoral Thesis
Press: Bauru.
Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB)
Defense date:
Examining board members:
Gustavo Pompermaier Garlet; Sandra Helena Penha de Oliveira; Camila de Oliveira Rodini Pegoraro; Maria Lucia Rubo de Rezende; Raquel Assed Bezerra da Silva
Advisor: Gustavo Pompermaier Garlet
Abstract

The osteoclast differentiation and activation are essential to bone tissue homeostasis and in the development of bone pathologies, which RANK/RANKL signaling molecules are the major osteoclastogenic factor. However, osteoclast co-stimulatory molecules, such as DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A, also present an important role in the osteoclastogenesis. However, the exact role and regulation of these molecules in human and mice periodontal diseases (PD) development have not completely known. Our aim was to investigate the pattern of osteoclast co-stimulatory expression (DAP-12, TREM-2, SIRP1, FcR, OSCAR and PIR-A) in human chronic periodontitis (CP), apart from analyze the kinetic of these molecules and their regulation by cytokines (TNF-, IFN-, IL-17 and IL-10) in the development of experimental periodontal disease in mice C57Bl/6 and knockout. Our results demonstrated that all osteoclast co-stimulatory molecules presented highly expressed in CP patients when compared with control. Similar results are presented about experimental PD, where all co-stimulatory molecules was presented highly expressed in infected mice when compared with control mice. We observed in TNFp55KO, IFNKO and IL17KO mice a decrease in PD scores and co-stimulatory molecules expression, the opposite of IL10KO mice. However, when we standardized the co-stimulatory molecules levels by the number of inflammatory cells, we found that TNF- and IL-17 are associated with increased expression of co-stimulatory molecules, while IFN- and IL-10 appear to negatively regulate the expression of such molecules. In conclusion, we demonstrated that osteoclast co-stimulatory molecules shown increased in human and experimental PD, and cytokines appear to modulate their expression by direct and indirect mechanisms, such as inflammatory cells migration to the PD infected tissue. (AU)

FAPESP's process: 08/11174-1 - KINETICS OF OSTEOCLAST CO-STIMULATORY MOLECULES THROUGHOUT EXPERIMENTAL PERIODONTITIS AND MICE AND ITS MODULATION BY CYTOKINES
Grantee:Carlos Eduardo Palanch Repeke
Support Opportunities: Scholarships in Brazil - Doctorate