This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The original Project 3 focused on polymicrobial infections inducing inflammation and bone loss using a murine calvarial model. It was designed to examine synergistic virulence effects of P. gingivalis, T. forsythensis, and T. denticola. Additionally, the aims were developed to determine the impact of acquired immune responses to infection and active immunity following immunization of the inflammation and tissue destruction. Following submission of the COBRE and prior to its funding in Sept. 2004, this research was funded as an R01 from the NIDCR. Thus, the COBRE grant provided the PI, Dr. Kesavalu, a ?Transition Award? to extend his research and contribute to submission of a 2nd R01 application. The funding provided support for a pilot study, initiated to document the ability to infect the oral cavity of rats with the polymicrobial consortium of P. gingivalis (Pg), T. denticola (Td), and T. forsythia (Tf) (Pg/Td/Tf). This was compared to the potential that incorporation of F. nucleatum (bridging and coaggregating pathogen) into this mixture (Pg/Td/Tf/Fn) would enhance the effectiveness of the infection regimen. Using an modified infection procedure, rats were challenged orally on 5 consecutive days with a 2% CMC solution containing a mixture of the microorganisms. The molar teeth were swabbed, DNA isolated from oral samples, and assessed using PCR for the presence of the bacteria. The results demonstrated seminal data that the rats were infected with the polymicrobial pathogenic consortia. Rats were euthanized, the gingival tissues collected and snap frozen in liquid nitrogen. Blood and rat jaws also were collected for serum IgG antibody and assessment of alveolar bone resorption. A significant serum antibody response to members of the polymicrobial infection was noted, supporting oral tissue infection and systemic challenge by the oral infection. Interestingly, the polymicrobial challenge with the Pg/Td/Tf/Fn consortium (5 days, 1 time during the 12 weeks), appeared to elicited substantially greater antibody. Alveolar bone loss in rats infected with these consortia demonstrated 2 primary findings. The single infection regimen with the Pg/Td/Tf challenged elicited minimal bone loss, supporting that a single challenge regimen is not sufficient to establish and maintain a disease process. However, the Pg/Td/Tf/Fn consortium, with a minimal infection challenge, induced significant bone loss, that was significantly greater than noted with any of the monoinfections, which had received the challenge multiple times during the 12 weeks. These findings provided additional preliminary data in support of an R01 application that is currently under review at the NIH.
The aims of this proposal include:
SPECIFIC AIM 1 : To determine the effect of n-3 PUFA to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis-T. forsythia-T. denticola in rats.
SPECIFIC AIM 2. To determine the effect of a dietary antioxidant supplement ?-lipoic acid and vitamin E (?-LA/VE) to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis, T. forsythia, and T. denticola in rats.
SPECIFIC AIM 3. To determine the effect of a potent anti-inflammatory/antioxidant natural dietary substance, curcumin, to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis, T. forsythia, and T. denticola in rats.
SPECIFIC AIM 4. To determine the effect of combinations of dietary anti-inflammatories/antioxidants as co-supplements to modulate or decrease periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis, T. forsythia, and T. denticola in rats.
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