Yu Y, Qiu L, Guo J, Yang D, Qu L, Yu J, Zhan F, Xue M, Zhong M
Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
Department of Oral Pathology, Central Laboratory, School of Stomatology, China Medical University, Shenyang, China.
Mol Oral Microbiol. 2015 Aug;30(4):295-306. doi: 10.1111/omi.12094. Epub 2015 Mar 9.
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.
牙髓卟啉单胞菌脂多糖（LPS）被认为与牙周病和根尖周病中骨吸收的进展相关。Wnt5a最近被认为参与炎症过程，但其作为牙髓卟啉单胞菌LPS诱导的成骨细胞介质的作用尚不清楚。 Tribbles同源物3（TRIB3）编码一种假激酶，在某些情况下与炎症有关。在这里，我们发现牙髓卟啉单胞菌LPS以剂量和时间依赖性方式诱导Wnt5a表达，并且它还上调了MC3T3-E1细胞中核因子-κB（NF-κB）的易位、磷酸化和转录活性。 Bay 11-7082阻断了牙髓卟啉单胞菌LPS诱导的NF-κB易位和Wnt5a表达。染色质免疫沉淀试验进一步证实，牙髓卟啉单胞菌LPS对Wnt5a的诱导是通过NF-κB p65亚基介导的。此外，在模拟时间10小时后，牙髓卟啉单胞菌LPS增加了成骨细胞中TRIB3的表达。TRIB3的过表达增强了NF-κB磷酸化和Wnt5a诱导，而TRIB3的敲低抑制了牙髓卟啉单胞菌LPS刺激的成骨细胞中NF-κB磷酸化和Wnt5a表达。这些结果表明，牙髓卟啉单胞菌LPS有能力促进小鼠成骨细胞中Wnt5a的表达，并且这种诱导主要由NF-κB途径介导。TRIB3似乎调节牙髓卟啉单胞菌LPS刺激的成骨细胞中Wnt5a的持续表达，以及调节NF-κB磷酸化。
