Blockade of TLR2 inhibits Porphyromonas gingivalis suppression of mineralized matrix formation by human dental pulp stem cells.
Blockade of TLR2 inhibits Porphyromonas gingivalis suppression of mineralized matrix formation by human dental pulp stem cells.
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DOI：
10.1016/j.joen.2011.03.013
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发表时间：
2011-06
影响因子：
4.2
通讯作者：
Glogauer, Michael
中科院分区：
文献类型：
--
作者：
Yamagishi, Valerie Tom-Kun;Torneck, Calvin D.;Friedman, Shimon;Huang, George T. -J;Glogauer, Michael
人牙髓干/祖细胞（Human dental pulp stem/progenitor cells，hDPSC）可分化为成牙本质细胞样细胞，表达牙本质涎磷蛋白（dentin sialophosphoprotein，DSPP）和骨钙素（osteocalcin，OCN），可用于牙本质再生。然而，根管中残留的细菌成分可能会抑制这种活性。本研究调查了牙龈卟啉单胞菌组分对刺激的hDPSC的DSPP和OCN表达的影响以及阻断TLR 2介导的牙龈卟啉单胞菌宿主识别的影响。将刺激的hDPSC暴露于不同浓度的牙龈卟啉单胞菌脂多糖（LPS），并测量DSPP和OCN的表达。在暴露于LPS之前，将类似组的刺激的hDPSC暴露于TLR 2阻断剂。暴露于5、10和20 μg/mL LPS的hDPSC表现出DSPP（分别为3.19 ± 0.18、2.60 ± 0.49和1.15 ± 0.29）和OCN（分别为3.51 ± 1.18、2.60 ± 0.67和1.66 ± 0.89）表达的剂量依赖性降低。暴露于20 μg/mL LPS后DSPP和OCN的表达显著低于未暴露的刺激细胞的测量值（方差分析和事后Tukey检验，P < .05）。使用细胞外和细胞内药物阻断TLR 2影响DSPP（4.67 ± 0.97和5.29 ± 1.66）和OCN（分别为5.25 ± 1.69和5.82 ± 2.38），表达水平与未暴露于20 µg/mL LPS的刺激细胞相当（DSPP和OCN分别为6.32 ± 2.47和4.70 ± 1.60）。证实了牙龈卟啉单胞菌对hDPSC形成矿化基质的抑制作用，并且这种抑制可以通过TLR 2阻断来缓和。
Human dental pulp stem/progenitor cells (hDPSC) can differentiate into odontoblast-like cells and express dentin sialophosphoprotein (DSPP) and osteocalcin (OCN); thus, they may be used to regenerate dentin. However, residual bacterial components in the root canal may suppress this activity. This study investigated the effect of a Porphyromonas gingivalis component on the expression of DSPP and OCN by stimulated hDPSCs and the influence of blockade of TLR2-mediated P. gingivalis host recognition. Stimulated hDPSCs were exposed to varying concentrations of P. gingivalis lipopolysaccharide (LPS), and the expression of DSPP and OCN was measured. Similar groups of stimulated hDPSCs were exposed to TLR2 blocking agents before exposure to LPS. hDPSCs exposed to 5, 10, and 20 µg/mL LPS exhibited a dose-dependent reduction in the expression of DSPP (3.19 ± 0.18, 2.60 ± 0.49, and 1.15 ± 0.29, respectively) and OCN (3.51 ± 1.18, 2.60 ± 0.67 and 1.66 ± 0.89, respectively). The expression of DSPP and OCN after exposure to 20 µg/mL of LPS was significantly lower than measured for unexposed stimulated cells (analysis of variance and post hoc Tukey test, P < .05). The blockade of TLR2 using an extra- and intracellular agent affected DSPP (4.67 ± 0.97 and 5.29 ± 1.66, respectively) and OCN (5.25 ± 1.69 and 5.82 ± 2.38, respectively) expression at levels comparable to stimulated cells unexposed to 20 µg/mL LPS (6.32 ± 2.47 and 4.70 ± 1.60 for DSPP and OCN, respectively). The suppressing effect of P. gingivalis on mineralized matrix formation by hDPSCs is confirmed, and this suppression can be moderated by TLR2 blockade.
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