rhHMGB1 drives osteoblast migration in a TLR2/TLR4- and NF-κB-dependent manner.
rhHMGB1 drives osteoblast migration in a TLR2/TLR4- and NF-κB-dependent manner.
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DOI：
10.1042/bsr20150239
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发表时间：
2016-01-07
影响因子：
4
通讯作者：
Chen JT
中科院分区：
文献类型：
--
作者：
Li MJ;Li F;Xu J;Liu YD;Hu T;Chen JT
本文报道了rhHMGB 1通过TLR 2或TLR 4激活NF-κB，可显著促进成骨细胞的迁移而不产生细胞毒性效应，提示HMGB 1在骨骼发育和骨修复中具有重要的功能作用。成骨细胞迁移在骨骼发育中具有重要意义。近年来，高迁移率族蛋白B1（HMGB 1）在软骨组织中高表达，参与软骨内骨化的调控。然而，HMGB 1是否可以调节成骨细胞的增殖和迁移，以及参与这一过程的细胞内信号通路知之甚少。在此，我们研究了重组人HMGB 1（rhHMGB 1）对大鼠成骨细胞增殖和迁移的影响，并研究了Toll样受体2（TLR 2）和TLR 4依赖的信号通路是否参与细胞内信号的调节。transwell小室法检测成骨细胞迁移能力，MTT法检测成骨细胞增殖能力。rhHMGB 1能显著促进成骨细胞的迁移而不抑制其增殖。同时，rhHMGB 1可增加核因子-κ B（NF-κB）p65的核转位。靶向TLR 2或TLR 4的siRNA构建体可显著抑制HMGB 1诱导的成骨细胞迁移和HMGB 1增强的NF-κB活化。总之，HMGB 1能显著促进成骨细胞的迁移，TLR 2/TLR 4依赖的NF-κB通路参与了HMGB 1诱导的成骨细胞迁移。
In this paper, we reported that rhHMGB1 could significantly enhance the migration of osteoblast without causing cytotoxic effects through the activation of NF-κB via TLR2 or TLR4, indicating a significant functional role for HMGB1 in skeletal development and bone restoration. Osteoblast migration is significant in skeletal development. Recently, high mobility group box 1 protein (HMGB1) has been shown to highly expressed in cartilage to regulate endochondral ossification. Nevertheless, whether HMGB1 can modulate osteoblast proliferation and migration is poorly understood, as well as the intracellular signalling pathways that are involved in this process. Herein, we examined the effects of recombinant human HMGB1 (rhHMGB1) on the proliferation and migration of rat osteoblasts and investigated whether Toll-like receptor 2 (TLR2)- and TLR4-dependent signalling pathways are involved in the regulation of intracellular signalling. A transwell chamber assay was used to evaluate the migration of osteoblasts and the MTT assay was used to assess osteoblast proliferation. rhHMGB1 could significantly promote the migration of osteoblasts without inhibiting their proliferation. Meanwhile, rhHMGB1 can increase the nuclear translocation of nuclear factor-kappa B (NF-κB) p65. Specific siRNA constructs that target TLR2 or TLR4 could markedly inhibit HMGB1-induced migration of osteoblasts and HMGB1-enhanced activation of NF-κB. Collectively, HMGB1 could significantly enhance the migration of osteoblasts in vitro, and TLR2/TLR4-dependent NF-κB pathways are involved in HMGB1-induced osteoblast migration.