The role of pro- and anti-inflammatory cytokines in alveolar bone repair process under homeostatic and infectious conditions: histomorphometric and molecular characterization in a experimental murine model

Abstract

Bone metabolism is influenced by endocrine, genetic and growth factors, besides regulatory molecules common to the bone and immune systems, such as cytokines. However, little is known about the mechanisms involved in alveolar bone repair, both in homeostatic conditions as infectious (as in experimental dry socket, which results in intense inflammatory response and in delayed repair process). Therefore, the objective of this project is to determine through histomorphometric and molecular characterization, the role of pro and anti-inflammatory, and extremes inflammatory genotypes (maximum and minimum) in alveolar bone repair in homeostatic and infectious conditions (experimental dry socket) by applying the model in mice of different strains: genetically deficient for TNF-a (p55KO) and IL-10 (IL-10KO) receptor and the control strain WT (C57Bl/6), and genetically selected for maximal (AIRmax) or minimal (AIRmin) inflammatory reaction. The different strains will be subdivide in control and experimental alveolitis groups (induced by the inoculation in alveolus of a suspension of bacterial culture containing microorganisms associated with human dry socket), and analyzed during the periods of 0, 7, 14 and 21 days. The samples will be subjected to histological processing and analyze by optical microscopy for histomorphometric characterization (qualitative and quantitative), and molecular analysis will be performed for quantification of mRNA of cytokines and bone formation and resorption markers using the RealTimePCR. The data will be statistically analyzed and compared between different strains, groups and time points. The joint analysis of these data will certainly contribute to improve the understanding of the molecular mechanisms involved in alveolar bone repair by promoting specific knowledge that can cooperate significantly to the future development of new strategies for diagnosis, prevention and therapy of bone pathologies. (AU)