Lipopolysaccharide enhances decorin expression through the Toll-like receptor 4, myeloid differentiating factor 88, nuclear factor-kappa B, and mitogen-activated protein kinase pathways in odontoblast cells.
Lipopolysaccharide enhances decorin expression through the Toll-like receptor 4, myeloid differentiating factor 88, nuclear factor-kappa B, and mitogen-activated protein kinase pathways in odontoblast cells.
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脂多糖通过 Toll 样受体 4、髓样分化因子 88、核因子 Kappa B 和丝裂原激活蛋白激酶途径增强成牙本质细胞中核心蛋白聚糖的表达。
DOI：
10.1016/j.joen.2011.12.021
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
He W, Qu T, Yu Q, Wang Z, Wang H, Zhang J,Smith AJ
中科院分区：
文献类型：
--
作者：
He W, Qu T, Yu Q, Wang Z, Wang H, Zhang J,Smith AJ
前言脂多糖（LPS）对成牙本质细胞的功能有调节作用。然而，LPS对成牙本质细胞作用的分子机制知之甚少。核心蛋白聚糖（DCN）是一种主要的基质蛋白聚糖，已知其影响牙齿的矿化。本研究旨在探讨LPS对成牙本质细胞DCN表达的调控作用及其可能的细胞内信号转导途径。方法采用实时荧光定量PCR（real-time polymerase chain reaction，PCR）和酶联免疫吸附试验（enzyme-linked immunosorbent assay，ELISA）检测LPS对小鼠成牙本质细胞系（odontoblast-lineage cells，OLC）DCN mRNA和蛋白表达的影响。采用实时荧光定量PCR、ELISA和荧光素酶活性测定等方法检测LPS诱导的DCN表达是否涉及TLR 4、髓样分化因子88（MyD 88）、核因子-κ B（NF-κB B）和丝裂原活化蛋白激酶（MAPK）通路。Western blot检测OLC中细胞外信号调节激酶（ERK）、p38和JNK的活性。DCN信使RNA被LPS以时间和剂量依赖的方式迅速诱导。用MyD 88抑制肽、TLR 4抗体或NF-κB或I κ B α（IκBα）特异性抑制剂预处理显著抑制LPS诱导的DCN表达。此外，LPS介导的OLC中κ B荧光素酶活性的增加被TLR 4、MyD 88和IκBα的显性负突变体的过表达抑制，但不被TLR 2的显性负突变体抑制。此外，LPS刺激激活ERK、p38和JNK MAPK通路。用ERK、p38和JNK MAPK通路的特异性抑制剂预处理OLC可显著抵消LPS诱导的DCN表达上调。结论LPS刺激可通过TLR 4、MyD 88、NF-κB B和MAPK通路上调成牙本质细胞DCN基因表达。
INTRODUCTIONLipopolysaccharide (LPS) has been shown to regulate the function of odontoblasts. However, the molecular mechanisms of the effect of LPS on odontoblasts are poorly understood. Decorin (DCN), one of the major matrix proteoglycans, is known to affect the mineralization of teeth. In this study, we investigated whether LPS can regulate the expression of DCN in odontoblasts and determined the intracellular signaling pathways triggered by LPS.METHODSThe DCN messenger RNA and protein expression changes in mouse odontoblast-lineage cells (OLCs) were detected by real-time polymerase chain reaction (PCR) analysis and enzyme-linked immunosorbent assay (ELISA). Whether TLR4, myeloid differentiating factor 88 (MyD88), nuclear factor-kappa B (NF-κB), or mitogen-activated protein kinase (MAPK) pathways were involved in the LPS-induced DCN expression was determined by examined real-time PCR, ELISA, and luciferase activity assay. The activation of extracellular signal-regulated kinase (ERK), p38, and JNK in OLCs was measured by Western blot analysis.RESULTSWe found that the mouse OLCs expressed DCN. DCN messenger RNA was rapidly induced by LPS in a time- and dose-dependent manner. Pretreatment with a MyD88 inhibitory peptide, a TLR4 antibody, or a specific inhibitor for NF-κB or I Kappa B alpha (IκBα) significantly inhibited LPS-induced DCN expression. Moreover, the LPS-mediated increase in κB-luciferase activity in OLCs was suppressed by the overexpression of dominant negative mutants of TLR4, MyD88, and IκBα but not by a dominant negative mutant of TLR2. In addition, LPS stimulation activated the ERK, p38, and JNK MAPK pathways. The pretreatment of OLCs with specific inhibitors of the ERK, p38, and JNK MAPK pathways markedly offset the LPS-induced up-regulation of DCN expression.CONCLUSIONSOur results show that LPS stimulation can up-regulate the gene expression of DCN via the TLR4, MyD88, NF-κB, and MAPK pathways in odontoblast cells.
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DOI：
10.1016/j.matbio.2008.11.003
发表时间：
2009-01
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Mochida Y;Parisuthiman D;Pornprasertsuk-Damrongsri S;Atsawasuwan P;Sricholpech M;Boskey AL;Yamauchi M
通讯作者：
Yamauchi M
影响因子：
4.1
作者：
Dejkhamron, Prapai;Thimmarayappa, Jamuna;Menon, Ram K.
通讯作者：
Menon, Ram K.
影响因子：
7.6
作者：
Staquet, M. -J.;Durand, S. H.;Farges, J. -C.
通讯作者：
Farges, J. -C.
影响因子：
7.6
作者：
WARFVINGE, J;DAHLEN, G;BERGENHOLTZ, G
通讯作者：
BERGENHOLTZ, G
影响因子：
7.6
作者：
Botero, T. M.;Son, J. S.;Noer, J. E.
通讯作者：
Noer, J. E.