Lipopolysaccharide differentially affects the osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells through Toll-like receptor 4 mediated nuclear factor κB pathway.
Lipopolysaccharide differentially affects the osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells through Toll-like receptor 4 mediated nuclear factor κB pathway.
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DOI：
10.1186/scrt456
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发表时间：
2014-05-27
影响因子：
7.5
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Li C;Li B;Dong Z;Gao L;He X;Liao L;Hu C;Wang Q;Jin Y
牙周炎是由细菌引发和持续的。然而，细菌性牙周炎的发病机制尚不清楚。我们假设细菌成分可以影响牙周组织中干细胞的功能。本研究比较了脂多糖（LPS）对人牙周膜干细胞（PDLSCs）和骨髓间充质干细胞（BMMSCs）成骨潜能的影响。收获人PDLSC和BMMSC，并通过茜素红S染色评估矿化结节形成。定量RT-PCR检测成骨相关基因的表达水平。Western blot检测Toll样受体4（TLR 4）及其下游信号通路的表达。采用茜素红S染色和qRT-PCR方法研究TLR 4及相关信号通路在LPS损伤人PDLSCs和BMMSCs成骨潜能中的作用。在成年Sprague-Dawley大鼠中诱导实验性牙周炎，并通过微型计算机断层扫描分析测量牙槽骨丢失。用免疫组化法检测碱性磷酸酶（ALP）的表达，用抗酒石酸酸性磷酸酶（TRAP）染色法检测破骨细胞的数量。LPS通过TLR 4调节核因子（NF）-κB途径抑制人PDLSCs的成骨分化，但对BMMSCs无影响。阻断TLR 4或NF-κB信号通路可部分逆转LPS诱导的大鼠牙周膜干细胞成骨能力的下降，防止LPS诱导的大鼠牙周炎牙槽骨丢失。在牙周膜中的ALP表达升高后，与抗TLR 4抗体或吡咯烷二硫代氨基甲酸酯治疗，而破骨细胞的数量组之间没有统计学意义。提示LPS可激活TLR 4调控的人PDLSCs NF-κB通路，从而降低其成骨潜能。阻断TLR 4或NF-κB途径可能为牙周炎的治疗提供新的途径。
Periodontitis is initiated and sustained by bacteria. However, the mechanism of bacteria induced periodontitis is still unknown. We hypothesized that bacterial components can affect the functions of stem cells in the periodontium. In this study, we comparatively investigated the influence of Lipopolysaccharide (LPS) on the osteogenesis potential of human periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMMSCs). Human PDLSCs and BMMSCs were harvested and mineralized nodule formation was assessed by alizarin red S staining. Expression level of osteogenic related gene was detected by quantitative RT-PCR (qRT-PCR). The expression of Toll-like receptor 4 (TLR4) and its downstream signaling pathway were examined by western blot. The role of TLR4 and related signaling pathway in LPS impairing the osteogenic potential of human PDLSCs and BMMSCs were also studied by alizarin red S staining and qRT-PCR. Experimental periodontitis was induced in adult Sprague–Dawley rats and the alveolar bone loss was measured by micro computed tomography analysis. The expression of alkaline phosphatase (ALP) was assessed by immunohistochemistry and the number of osteoclasts was shown by Tartrate-resistant acid phosphatase (TRAP) staining. LPS decreased the osteogenic differentiation of human PDLSCs through TLR4 regulated nuclear factor (NF)-κB pathway, but not for BMMSCs. Blocking TLR4 or NF-κB signaling partially reversed the decreased osteogenic potential of PDLSCs and prevented the alveolar bone loss caused by LPS experimental periodontitis in rats. The ALP expression in the periodontal ligament was elevated after treatment with anti-TLR4 antibody or pyrrolidinedithiocarbamate, whereas there was no statistical significance among groups for the number of osteoclasts. These data suggest that LPS can activate TLR4 regulated NF-κB pathway of human PDLSCs, thus decreasing their osteogenic potential. Blockage of TLR4 or NF-κB pathway might provide a new approach for periodontitis treatment.
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在间充质基质细胞衍生的骨基因生成剂中，长时间暴露于细菌毒素下调Toll样受体的表达。
影响因子：
--
作者：
Mo, Irene Fung Ying;Yip, Kevin Hak Kong;Chan, Wing Keung;Law, Helen Ka Wai;Lau, Yu Lung;Chan, Godfrey Chi Fung
通讯作者：
Chan, Godfrey Chi Fung
影响因子：
4.3
作者：
Raicevic, Gordana;Najar, Mehdi;Lagneaux, Laurence
通讯作者：
Lagneaux, Laurence
影响因子：
4.8
作者：
Gilbert, L;He, XF;Nanes, MS
通讯作者：
Nanes, MS
DOI：
10.1073/pnas.1018501108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Glass, Graeme E.;Chan, James K.;Nanchahal, Jagdeep
通讯作者：
Nanchahal, Jagdeep
影响因子：
4.3
作者：
Kawaguchi, H;Hirachi, A;Kurihara, H
通讯作者：
Kurihara, H