Continuous application of compressive force induces fusion of osteoclast-like RAW264.7 cells via upregulation of RANK and downregulation of LGR4
Continuous application of compressive force induces fusion of osteoclast-like RAW264.7 cells via upregulation of RANK and downregulation of LGR4
复制标题
DOI：
10.1016/j.lfs.2018.03.038
复制
发表时间：
2018-05-15
期刊：
影响因子：
6.1
通讯作者：
Shimizu, Noriyoshi
中科院分区：
文献类型：
--
作者：
Matsuike, Rieko;Tanaka, Hideki;Shimizu, Noriyoshi
目的：在正畸治疗中，促进牙槽骨在压缩力（CF）作用下的破骨细胞骨吸收是影响牙齿运动的重要因素。本研究探讨CF刺激对RAW264.7细胞由前体细胞向成熟破骨细胞分化的影响。主要方法：在细胞核因子KB （RANK）配体受体激活剂（RANKL）存在或不存在的情况下，用96孔板孔中增加培养基体积产生的0.3、0.6或1.1 g/cm(2) cf连续刺激细胞4天。主要结论:当着RANKL的面，与0.3 g/cm(2) CF相比，0.6和1.1 g/cm(2) CF增加了抗酒石酸酸性磷酸酶（TRAP）阳性的多核细胞数量以及树突状细胞特异性跨膜蛋白（DC-STAMP）和破骨细胞刺激跨膜蛋白（OC-STAMP）的mRNA水平。RANK mRNA水平上调，而富含赖氨酸的含有重复的g蛋白偶联受体（LGR）4-另一RANKL受体的mRNA水平下调0.6和1.1 g/cm(2)。与不含RANKL时的0.3 g/cm(2)CF相比。在RANKL存在下，活化T细胞核易位因子（NFAT）cl的核易位细胞比例分别增加0.6和1.1 g/cm(2) CF。意义：持续应用CF通过增强DC-和OC-STAMP的表达以及NFATc1的核易位，诱导RAW264.7细胞向trap阳性的多核细胞分化。这可能是由于cf诱导的RANK升高和LGR4表达降低所致。
Aims: During orthodontic treatment, facilitating osteoclastic bone resorption in the alveolar bone exposed to the compressive force (CF) is an important factor for tooth movement. The present study investigated the effect of CF stimulation on the differentiation of RAW264.7 cells from precursors to mature osteoclasts.Main methods: The cells were continuously stimulated with 0.3, 0.6, or 1.1 g/cm(2) CF-which was generated by increasing the volume of culture medium in the wells of a 96-well plate-in the presence or absence of receptor activator of nuclear factor KB (RANK) ligand (RANKL) for 4 days.Key findings: In the presence of RANKL, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and the mRNA levels of dendritic cell-specific transmembrane protein (DC-STAMP) and osteoclast-stimulatory transmembrane protein (OC-STAMP) were increased by application of 0.6 and 1.1 g/cm(2) CF as compared to 0.3 g/cm(2) CF. The mRNA level of RANK was upregulated whereas that of leucine-rich repeat-containing G-protein-coupled receptor (LGR)4-another RANKL receptor was downregulated by 0.6 and 1.1 g/ cm(2) CF as compared to 0.3 g/cm(2 )CF in the absence of RANKL. The proportion of cells with nuclear translocation of the nuclear translocation of nuclear factor of activated T cells (NFAT)cl was increased by 0.6 and 1.1 g/cm(2) CF in the presence of RANKL.Significance: Continuous application of CF induced the differentiation of RAW264.7 cells into TRAP-positive multinuclear cells by enhancing the expression of DC- and OC-STAMP and the nuclear translocation of NFATc1. This may result from the CF-induced increase in RANK and decrease in LGR4 expression.