title: Protective role of osteopontin in endodontic infection.
abstract: Endodontic infections are polymicrobial infections resulting in bone destruction and tooth loss. The host response to these infections is complex, including both innate and adaptive mechanisms. Osteopontin (OPN), a secreted, integrin-binding protein, functions in the regulation of immune responses and enhancement of leucocyte migration. We have assessed the role of OPN in the host response to endodontic infection using a well-characterized mouse model. Periapical bone loss associated with endodontic infection was significantly more severe in OPN-deficient mice compared with wild-type 3 weeks after infection, and was associated with increased areas of inflammation. Expression of cytokines associated with bone loss, interleukin-1alpha (IL-1alpha) and RANKL, was increased 3 days after infection. There was little effect of OPN deficiency on the adaptive immune response to these infections, as there was no effect of genotype on the ratio of bacteria-specific immunoglobulin G1 and G2a in the serum of infected mice. Furthermore, there was no difference in the expression of cytokines associated with T helper type 1/type2 balance: IL-12, IL-10 and interferon-gamma. In infected tissues, neutrophil infiltration into the lesion area was slightly increased in OPN-deficient animals 3 days after infection: this was confirmed by a significant increase in expression of neutrophil elastase in OPN-deficient samples at this time-point. We conclude that OPN has a protective effect on polymicrobial infection, at least partially because of alterations in phagocyte recruitment and/or persistence at the sites of infection, and that this molecule has a potential therapeutic role in polymicrobial infections.
authors.affiliation: Department of Cytokine Biology, The Forsyth Institute, Boston, MA 02115, USA. srittling@forsyth.org
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rittling
authors.forename: Craig
authors.initials: C
authors.lastname: Zetterberg
authors.forename: Kader
authors.initials: K
authors.lastname: Yagiz
authors.forename: Stephen
authors.initials: S
authors.lastname: Skinner
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimura
authors.forename: Hajime
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D016301:Alveolar Bone Loss / Q000235:genetics; D000818:Animals; D001424:Bacterial Infections / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007109:Immunity; D007136:Immunoglobulins / Q000097:blood; D019272:Leukocyte Elastase / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010485:Periapical Periodontitis / Q000235:genetics; D011671:Pulpitis; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D053245:RANK Ligand; D053495:Osteopontin; D019272:Leukocyte Elastase