Evaluation of αLphav Integrin Role in Mouse Model Induced Periapical Periodontitis
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CitationAllahem, Ziyad. 2016. Evaluation of αLphav Integrin Role in Mouse Model Induced Periapical Periodontitis. Doctoral dissertation, Harvard School of Dental Medicine.
Background: alphav (av) integrin is the most common integrin alpha subunit, it is expressed in different cells and involved in many cellular process including adhesion, migration, survival and growth factor signaling. alphav on immune cells has a role in promoting T regulatory (Treg) cells production and differentiation of T helper 17 (Th17) through activating TGF-beta as shown in conditional knockout of alphav in immune cells. Osteopontin (OPN) is a ligand for alphav and involved in modulation of inflammation through its interaction with alphav in immune cells. OPN has been shown to have a protective role in endodontic infection, so we predict alphav to have similar role. The aim of the study is to establish the role of αv integrin in the immune response to endodontic polymicrobial infection, using an established mouse model of endodontic infection
Methods: alphavfl/fl mice were mated with mice expressing Cre under the control of the Tie2 promoter, which is expressed in all cells of the hematopoietic lineage as well as in endothelial cells. These mice were subjected to pulp exposure and infection with a mixture of four endodontic pathogens. Bone loss was assessed 0, 7, 14, and 21 days after infection using micro CT. Inflammation and neutrophils enumeration in periapical area evaluated using immunohistochemistry, also osteoclast presence in periapical area examined with TRAP staining. Microarray and qPCR used to investigate cellular and cytokines activity changes. Blood plasma collected from mice during sacrificing was evaluated using ELISA for level of IgG’s and antibody activity against the specific bacteria used for the infection.
Results: Lack of alphav expression was confirmed on neutrophils by FACS. Twenty-one days after pulp exposure and infection with oral pathogens, 6 of 16 av-tie2cre KO mice developed swelling and abscesses in the mandible, while no abscesses were observed in control mice. However, the periapical bone resorption was similar in the two groups. Strikingly, ectopic bone formation on the buccal and lingual aspects of the mandibular surface was observed only in the av-tie2cre animals, suggesting a severe disruption of bone turnover caused by the inflammatory process in these animals. Neutrophils showed decrease in number in periapical area and microarray and the observe disseminating infection suggested a B cells defect either in function or migration.
Conclusions: Together, these results demonstrate a critical role for the alphav integrin in the suppression of inflammation during the process of endodontic infection.
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