RANKL deletion in periodontal ligament and bone lining cells blocks orthodontic tooth movement.
RANKL deletion in periodontal ligament and bone lining cells blocks orthodontic tooth movement.
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RANKL在牙周膜和骨衬细胞中的缺失阻碍正畸牙齿移动。
DOI：
10.1038/s41368-017-0004-8
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发表时间：
2018-02-26
影响因子：
14.9
通讯作者：
Graves DT
中科院分区：
文献类型：
--
作者：
Yang CY;Jeon HH;Alshabab A;Lee YJ;Chung CH;Graves DT
响应正畸力的骨重塑过程需要破骨细胞的活性，以允许牙齿沿所施加的力的方向移动。核因子-κB 配体受体激活剂 (RANKL) 对于这一过程至关重要，尽管其响应正畸力的细胞来源尚未确定。正畸牙齿移动被认为是一种无菌炎症过程，由白细胞（包括 T 和 B 淋巴细胞）刺激，推测这些白细胞会刺激骨吸收。我们通过他莫昔芬诱导 RANKL 缺失确定牙周膜和骨衬细胞是否是 RANKL 的重要来源，其中 Cre 重组酶由实验小鼠 Col1α1 基因的 3.2 kb 报告元件驱动 (Col1α1.CreERTM+.RANKLf/f)，并将结果与同窝对照 (Col1α1.CreERTM−.RANKLf/f) 进行比较。通过对 Col1α1.CreERTM+.ROSA26 报告小鼠的检查，我们发现他莫昔芬诱导的 Cre 重组酶的组织特异性主要存在于牙周膜和骨衬细胞中。令人惊讶的是，我们发现实验小鼠的大部分正畸牙齿移动和破骨细胞的形成受到阻碍，牙周膜间隙也减少。因此，我们首次证明牙周膜和骨衬细胞产生的 RANKL 为响应正畸力的牙齿移动和破骨细胞生成提供了主要驱动力。已鉴定出细胞和组织可产生正畸患者骨重塑所必需的信号分子。当定向机械力施加到牙齿上时，会引发变化以重塑牙齿周围的骨骼。费城宾夕法尼亚大学牙科医学院的研究人员在达纳·格雷夫斯 (Dana Graves) 的带领下，对小鼠进行了基因改造，以去除“RANKL”——一种被认为是骨骼分解介质的蛋白质。研究小组发现，负责产生 RANKL 的免疫细胞主要存在于连接牙根和骨脊的组织中，骨脊包含牙槽和排列在骨头上的保护细胞。去除 RANKL 会损害牙齿响应外部定向力而移动的能力。这项研究提供了对 RANKL 产生与正畸牙齿移动之间关系的见解。
The bone remodeling process in response to orthodontic forces requires the activity of osteoclasts to allow teeth to move in the direction of the force applied. Receptor activator of nuclear factor-κB ligand (RANKL) is essential for this process although its cellular source in response to orthodontic forces has not been determined. Orthodontic tooth movement is considered to be an aseptic inflammatory process that is stimulated by leukocytes including T and B lymphocytes which are presumed to stimulate bone resorption. We determined whether periodontal ligament and bone lining cells were an essential source of RANKL by tamoxifen induced deletion of RANKL in which Cre recombinase was driven by a 3.2 kb reporter element of the Col1α1 gene in experimental mice (Col1α1.CreERTM+.RANKLf/f) and compared results with littermate controls (Col1α1.CreERTM−.RANKLf/f). By examination of Col1α1.CreERTM+.ROSA26 reporter mice we showed tissue specificity of tamoxifen induced Cre recombinase predominantly in the periodontal ligament and bone lining cells. Surprisingly we found that most of the orthodontic tooth movement and formation of osteoclasts was blocked in the experimental mice, which also had a reduced periodontal ligament space. Thus, we demonstrate for the first time that RANKL produced by periodontal ligament and bone lining cells provide the major driving force for tooth movement and osteoclastogenesis in response to orthodontic forces. Cells and tissues have been identified that produce a signaling molecule essential for bone remodeling in orthodontic patients. Directional mechanical force, when applied to teeth, instigates changes to remodel the bone around the tooth. Researchers from the University of Pennsylvania School of Dental Medicine in Philadelphia, led by Dana Graves, genetically altered mice to remove ‘RANKL’, a protein thought to be a mediator in the breakdown of bone. The team found that the immune cells responsible for producing RANKL are primarily found in the tissue connecting tooth roots to the ridges of bone containing the tooth sockets and the protective cells that line the bones. Removing RANKL impaired the ability of the teeth to move in response to external directional force. This study provides insights into the relationship between RANKL production and orthodontic tooth movement.
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影响因子：
4.1
作者：
Elefteriou F;Yang X
通讯作者：
Yang X
影响因子：
3.3
作者：
Chen, Yi-Jyun;Shie, Ming-You;Kao, Chia-Tze
通讯作者：
Kao, Chia-Tze
影响因子：
7.6
作者：
Kanzaki, H;Chiba, M;Mitani, H
通讯作者：
Mitani, H
DOI：
10.1196/annals.1365.035
发表时间：
2006-01-01
期刊：
WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC, ENDOCRINE, AND REPRODUCTIVE ISSUES
影响因子：
--
作者：
Hadjidakis, Dimitrios J.;Androulakis, Ioannis I.
通讯作者：
Androulakis, Ioannis I.
影响因子：
3
作者：
BEERTSEN, W
通讯作者：
BEERTSEN, W