title: TRIB3 mediates the expression of Wnt5a and activation of nuclear factor-κB in Porphyromonas endodontalis lipopolysaccharide-treated osteoblasts.
abstract: Porphyromonas endodontalis lipopolysaccharide (LPS) is considered to be correlated with the progression of bone resorption in periodontal and periapical diseases. Wnt5a has recently been implicated in inflammatory processes, but its role is unclear as a P. endodontalis LPS-induced mediator in osteoblasts. Tribbles homolog 3 (TRIB3) encodes a pseudokinase and has been linked to inflammation in certain situations. Here, we found that P. endodontalis LPS induced Wnt5a expression in a dose- and time-dependent manner and it also upregulated translocation, phosphorylation and transcriptional activity of nuclear factor-κB (NF-κB) in MC3T3-E1 cells. Bay 11-7082 blocked the translocation of NF-κB and Wnt5a expression induced by P. endodontalis LPS. Chromatin immunoprecipitation assay further established that induction of Wnt5a by P. endodontalis LPS was mediated through the NF-κB p65 subunit. Additionally, P. endodontalis LPS increased expression of TRIB3 in osteoblasts after 10 h simulated time. Overexpression of TRIB3 enhanced NF-κB phosphorylation and Wnt5a induction, whereas knockdown of TRIB3 inhibited NF-κB phosphorylation and Wnt5a expression in P. endodontalis LPS-stimulated osteoblasts. These results suggest that P. endodontalis LPS has the ability to promote the expression of Wnt5a in mouse osteoblasts, and this induction is mainly mediated by NF-κB pathway. TRIB3 seems to modulate the sustained expression of Wnt5a in osteoblasts stimulated by P. endodontalis LPS, as well as regulating NF-κB phosphorylation.
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: L
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: L
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhan
authors.affiliation: Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: M
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Oral Pathology, Central Laboratory, School of Stomatology, China Medical University, Shenyang, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D055785:Gene Knockdown Techniques; D008070:Lipopolysaccharides / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D045202:Porphyromonas endodontalis / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse
keywords: apical periodontitis; cell signaling; inflammatory response; lipopolysaccharide