GSK3 inhibition protects against gum disease

Sep 20 2012

By Sarah Guy, medwireNews Reporter

Treatment with the cell-permeable glycogen synthase kinase (GSK)-3β-specific enzyme inhibitor SB216763 successfully suppresses alveolar bone loss in mice infected with the main periodontal pathogen, Porphyromonas gingivalis, report researchers.

The finding indicates that GSK3β enzyme inhibition in humans may be a method of protecting against the chronic, systemic sequelae associated with periodontal diseases, they add in Molecular Medicine.

"The traditional approach to dealing with periodontal disease is to prevent plaque from forming at the gum-line or prevent the consequences of periodontal disease progression," said co-researcher David Scott (University of Louisville, Kentucky, USA) in a press statement.

"Our approach manipulates a natural mechanism within our bodies to prevent inflammation and subsequent degradation when exposed to the bacterium P. gingivalis," he added.

Scott and colleagues orally infected five mice with P. gingivalis and compared rates of alveolar bone loss with five sham-infected and five vehicle-only-exposed controls. The vehicle (SB216763 10 mg/kg) was administered to the P. gingivalis group 1 day prior to being infected and every other day thereafter until sacrifice.

At 6 weeks after infection, methylene blue/eosin staining revealed that alveolar bone loss was significantly greater in mice infected with P. gingivalis than sham-infected and vehicle-only mice.

Critically, write the researchers, pharmaceutical inhibition of GSK3β via SB216763 "completely abrogated" this pathogen-induced hard tissue destruction, reducing it to control levels.

Furthermore, neutrophil infiltration into gingival tissues and the pro-inflammatory cytokine interleukin (IL)-17 were both reduced after GSK3β inhibition, indicating overall reduction of periodontal inflammation.

GSK3β is known to induce inflammation during bacterial infections, thus inhibiting it from its normal function stops this process in P. gingivalis-infected mice, explained Scott.

"Increasing evidence suggests that periodontitis is associated with increased risk of vascular diseases (including coronary artery disease and stroke), diabetes mellitus, lung diseases (COPD [chronic obstructive pulmonary disease] and pneumonia), and pre-term delivery," say the researchers.

"Thus, the potential significance and impact of controlling or reducing pathogen-induced periodontal diseases is enormous," they conclude.

Potential side effects for humans will need to be assessed in future studies, they recommend.

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