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TPCA‐1 negatively regulates inflammation mediated by NF‐κB pathway in mouse chronic periodontitis model
Author(s) -
Wang Bo,
Bai Shizhu,
Wang Jiang,
Ren Nan,
Xie Rui,
Cheng Geng,
Yu Yan
Publication year - 2021
Publication title -
molecular oral microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 77
eISSN - 2041-1014
pISSN - 2041-1006
DOI - 10.1111/omi.12335
Subject(s) - osteoclast , periodontitis , rankl , inflammation , chronic periodontitis , rank ligand , tumor necrosis factor alpha , nf κb , bone resorption , immunology , cancer research , medicine , activator (genetics) , receptor
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.