Co-regulation of LPS and tensile strain downregulating osteogenicity via c-fos expression
Co-regulation of LPS and tensile strain downregulating osteogenicity via c-fos expression
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LPS 和拉伸应变通过 c-fos 表达共同调节成骨性
DOI：
10.1016/j.lfs.2013.05.015
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发表时间：
2013-07-19
期刊：
影响因子：
6.1
通讯作者：
Hu, Rongdang
中科院分区：
文献类型：
--
作者：
Wang, Yi;Wang, Haiyan;Hu, Rongdang
目的：众所周知，正畸力会加重炎症引起的牙周组织破坏，但其潜在机制尚未阐明。本研究探讨炎症和外力如何共同调节牙周组织损伤。主要方法：用100 ng/ml牙龈卟啉单胞菌（Porphyromonas gingivalis，Pg）-LPS刺激RAW264.7巨噬细胞的条件培养液预处理MC 3 T3-E1成骨细胞。通过ELISA分析条件培养基中的白细胞介素-1 β（IL-1 β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）。然后使成骨细胞经受拉伸应变（0.5 Hz; 1000 mu或3000 mu）0 min、5 min、15 min、30 min、1 h、3 h和6 h。分析培养物中c-fos的mRNA和蛋白水平。关键发现：（Pg）-LPS以剂量和时间依赖性方式刺激RAW 264.7细胞分泌所有三种细胞因子。（Pg）-LPS刺激细胞的培养基诱导c-fos表达增加10倍，3 h后降至4倍平台。相反，对照组成骨细胞ALP活性在前60 min内下降，然后在接下来的4 h内恢复。预处理与条件培养基产生相同的初始减少在拉伸应变，但防止recovery.Significance：我们的研究表明，第一次，炎症和拉伸应变对成骨的抑制作用与c-fos表达的上调。此外，炎症可能会降低成骨细胞在持续拉伸应力下恢复其成骨能力的能力，并导致牙周组织损伤。(C)2013 Elsevier Inc. All rights reserved.
Aims: Orthodontic forces are known to aggravate inflammation-induced destruction of the periodontium, but the underlying mechanism has not been elucidated. The present study investigates how inflammation and forces co-regulate periodontium damage.Main methods: Cultures of MC3T3-E1 osteoblasts were pre-treated with conditioned medium from RAW264.7 macrophages exposed to 100 ng/ml Porphyromonas gingivalis (Pg)-LPS. Conditioned medium was analyzed by ELISA for interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Osteoblasts were then subjected to tensile strain (0.5 Hz; 1000 mu or 3000 mu) for 0 min, 5 min, 15 min, 30 min, 1 h, 3 h, and 6 h. The cultures were analyzed for mRNA and protein levels of c-fos. Cells were also analyzed for alkaline phosphatase (ALP) activity.Key findings: (Pg)-LPS stimulated the secretion of all three cytokines from RAW264.7 cells in a dose- and time-dependent manner. Medium from (Pg)-LPS stimulated cells induced a 10-fold increase in c-fos expression, which decreased to a 4-fold plateau after 3 h. In contrast, ALP activity of control osteoblasts decreased during the first 60 min, then recovered over the next 4 h. Pretreatment with conditioned medium generated the same initial decrease during tensile strain but prevented the recovery.Significance: Our study showed, for the first time, that the inhibitory effect of inflammation and tensile strain on osteogenicity is associated with the upregulation in c-fos expression. In addition, inflammation may reduce the ability of osteoblasts to restore their osteogenic capacity during sustained tensile stress and contribute to periodontium damage. (C) 2013 Elsevier Inc. All rights reserved.