Molecular mechanisms of the inhibitory effect of lipopolysaccharide (LPS) on osteoblast differentiation

被引：174

作者：

Bandow, Kenjiro ^{[1
]}

Maeda, Aya ^{[2
]}

Kakimoto, Kyoko ^{[1
]}

Kusuyama, Joji ^{[1
]}

Shamoto, Mitsuo ^{[1
]}

Ohnishi, Tomokazu ^{[1
]}

Matsuguchi, Tetsuya ^{[1
]}

机构：

[1] Kagoshima Univ, Dept Oral Biochem, Field Dev Med, Grad Sch Med & Dent Sci, Kagoshima 8908544, Japan

[2] Kagoshima Univ, Dept Orthodont, Field Dev Med, Grad Sch Med & Dent Sci, Kagoshima 8908544, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 402卷 / 04期

关键词：

Osteoblasts; LPS; Myd88; Cot/Tpl2; TLR4; TOLL-LIKE RECEPTORS; CELL-DIFFERENTIATION; BONE-RESORPTION; TNF-ALPHA; PORPHYROMONAS-GINGIVALIS; SIGNAL-TRANSDUCTION; EXPRESSION; PROTEIN; ACTIVATION; INDUCTION;

D O I：

10.1016/j.bbrc.2010.10.103

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Osteoblasts express Toll like receptor (TLR) 4 and produce osteoclast-activating cytokines in response to the stimulation by lipopolysaccharide (LPS) It has recently been reported that LPS exerts an inhibitory effect on osteoblast differentiation into osteocytes However the molecular mechanisms of this inhibitory effect remain ambiguous The downstream signals of TLR4 are mediated by adaptor molecules including myeloid differentiation factor 88 (MyD88) leading to the activation of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinases (ERKs) whose activation by LPS requires the upstream serine/threonine kinase Cot/Tpl2 To determine the signal molecules responsible for the inhibitory effects of LPS on osteoblast differentiation we examined the in vitro differentiation of the primary osteoblasts from myd88(-/-) and cot/tpl2(-/-) mice The matrix mineralization by the wild-type and cot/tpl2(-/-) osteoblasts was significantly inhibited by LPS whereas that of myd88(-/-) was not affected During differentiation LPS suppressed the mRNA expression of runt related transcription factor 2 (Runx2) osterix (Sp7) and activating transcription factor 4 (ATF4) in the wild-type but not in the myd88-/- osteoblasts The inhibitory effect of LPS on the mRNA expression of these transcription factors was absent in the early phase but partially impaired in the late phase of differentiation in the cot/tpl2(-/-) osteoblasts Thus the inhibitory effect of LPS on osteoblast differentiation is Myd88-dependent whereas the degree of its requirement for Cot/Tpl2 vanes depending on the differentiation phase (C) 2010 Elsevier Inc All rights reserved

引用

页码：755 / 761

页数：7

共 39 条

[1]

Substance P enhances the inhibition of osteoblastic cell differentiation induced by lipopolysaccharide from Porphyromonas gingivalis [J].