A novel IkB kinase inhibitor attenuates ligature‐induced periodontal disease in mice

Backgrounds and Objectives IMD‐0354 is a novel I kappa‐B kinase (IKK) inhibitor, which regulates inflammation. The purpose of this study was to examine the effect of the reagent on bone loss for ligature‐induced periodontitis. Material and Methods We ligated around the upper right second molars of 8‐week‐old C57BL/6J mice in the split‐mouth model. The test mice were injected intraperitoneally with IMD‐0354 before the placement of the ligature. The control mice were injected intraperitoneally with 0.5% carboxymethylcellulose (CMC) as vehicle before the placement of the ligature. To determine the optimum concentration of the reagent on ligature‐induced periodontitis in the mice, we examined the effect of three types of concentration, which were 1, 5, and 10 mg/kg of IMD‐0354, as a preliminary experiment. After we determined 10 mg/kg as the optimum concentration for the IMD group by micro‐CT analysis, both the IMD and CMC groups (n = 15 each in total, including all the analyses) were subdivided into two small groups, respectively, for further analyses: I group (unligated side of IMD group), IL group (ligated side of IMD group), C group (unligated side of CMC group) and CL group (ligated side of CMC group). The mice in the IMD and CMC groups were treated with each reagent daily and sacrificed 8 days after the ligation. For assessment of bone resorption, we performed micro‐CT and histological analyses. We also carried out real‐time PCR to investigate proinflammatory and bone metabolic markers. Results There were significant differences for linear bone loss and volumetric parameter in the test (IMD) group compared to the control (CMC) group 8 days after ligation. In terms of the mRNA expression level of gingival tissue, the level of RANKL was significantly suppressed in the IMD group compared to the CMC group. IMD‐0354 also tended to suppress the levels of interleukin‐1 beta, tumor necrosis factor‐alpha, and osteoprotegerin. For histological analysis, the relative numbers of TRAP‐positive multinucleated cells decreased significantly in the IMD group compared to the CMC group. Conclusion IMD‐0354 regulated bone resorption by ligature‐induced periodontitis, and it is suggested that the inhibition of IKK via down‐regulation of NF kappa‐B may provide periodontal patients with an effective approach to prevent or suppress the disease.