Low-intensity pulsed ultrasound (LIPUS) inhibits LPS-induced inflammatory responses of osteoblasts through TLR4-MyD88 dissociation
Low-intensity pulsed ultrasound (LIPUS) inhibits LPS-induced inflammatory responses of osteoblasts through TLR4-MyD88 dissociation
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DOI：
10.1016/j.bone.2013.09.018
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发表时间：
2014-01-01
期刊：
影响因子：
4.1
通讯作者：
Matsuguchi, Tetsuya
中科院分区：
文献类型：
--
作者：
Nakao, Juna;Fujii, Yasuyuki;Matsuguchi, Tetsuya
先前的报告表明，成骨细胞对机械力敏感。低强度脉冲超声 (LIPUS) 诱导成骨细胞分化，是一种既定的骨折治疗方法。在这里，我们研究了 LIPUS 如何影响成骨细胞对 LPS 的炎症反应。 LPS 在小鼠成骨细胞系和颅骨来源的成骨细胞中快速诱导多种趋化因子的 mRNA 表达，包括 CCL2、CXCL1 和 CXCL10。 LIPUS 同时处理显着抑制 LPS 对 CXCL1 和 CXCL10 mRNA 的诱导。在 LIPUS 处理的成骨细胞中，LPS 诱导的 ERK、p38 激酶、MEK1/2、MKK3/6、IKK、TBK1 和 Akt 磷酸化降低。此外，LIPUS通过LPS抑制NF-κB反应元件和干扰素敏感反应元件(ISRE)的转录激活。在瞬时转染实验中，LIPUS 显着抑制 TLR4-MyD88 复合物的形成。因此，LIPUS 通过抑制 TLR4 信号转导对 LPS 刺激的成骨细胞发挥抗炎作用。 (C) 2013 Elsevier Inc. 保留所有权利。
Previous reports have shown that osteoblasts are mechano-sensitive. Low-intensity pulsed ultrasound (LIPUS) induces osteoblast differentiation and is an established therapy for bone fracture. Here we have examined how LIPUS affects inflammatory responses of osteoblasts to LPS. LPS rapidly induced mRNA expression of several chemokines including CCL2, CXCL1, and CXCL10 in both mouse osteoblast cell line and calvaria-derived osteoblasts. Simultaneous treatment by LIPUS significantly inhibited mRNA induction of CXCL1 and CXCL10 by LPS. LPS-induced phosphorylation of ERKs, p38 kinases, MEK1/2, MKK3/6, IKKs, TBK1, and Akt was decreased in LIPUS-treated osteoblasts. Furthermore, LIPUS inhibited the transcriptional activation of NF-kappa B responsive element and Interferon-sensitive response element (ISRE) by LPS. In a transient transfection experiment, LIPUS significantly inhibited TLR4-MyD88 complex formation. Thus LIPUS exerts anti-inflammatory effects on LPS-stimulated osteoblasts by inhibiting TLR4 signal transduction. (C) 2013 Elsevier Inc. All rights reserved.