TPCA-1 negatively regulates inflammation mediated by NF-κB pathway in mouse chronic periodontitis model.

Abstract

The dysregulation of immune system plays a crucial function in periodontitis development. Pro-inflammatory cytokines are thought to be critical for the generation and development of periodontitis. The enhanced activity of osteoclasts contributes to periodontitis pathogenesis. Nuclear factor-κB (NF-κB) signaling pathway directly enhances osteoclast differentiation and maturation. 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) is a IκB kinases (IKK) inhibitor. This research aimed to investigate whether TPCA-1 had influence on the pathogenesis of chronic periodontitis. Mouse chronic periodontitis was induced by an in vivo ligature-induced periodontitis model. TPCA-1 was intravenously injected into mice after chronic periodontitis induction. Bone marrow-derived macrophages were cultured in macrophage colony-stimulating factor (M-CSF)-conditioned media with receptor activator of nuclear factor-kappa B ligand (RANKL) induce in vitro osteoclast differentiation. Western blot was used to analyze protein levels and mRNA levels were analyzed through qRT-PCR. TPCA-1 promoted osteoclastogenesis and osteoclast-related gene expression in vitro. The production of pro-inflammatory cytokines in osteoclasts induced by lipopolysaccharides was inhibited by TPCA-1 in vitro. In vitro TPCA-1 treatment inhibited Aggregatibacter actinomycetemcomitans (A.a)-induced expression of pro-inflammatory cytokines and NF-κB signal activation in osteoclasts. The induction of chronic periodontitis was inhibited by the absence of IKKb in mice. This research demonstrates that the treatment of TPCA-1 negatively regulates inflammation response and inhibits the osteoclastogenesis through the inactivation of NF-κB pathway in mouse chronic periodontitis model.