Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Int J Oral Sci. 2018 Feb 26;10(1):3. doi: 10.1038/s41368-017-0004-8.
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.CreER.RANKL) and compared results with littermate controls (Col1α1.CreER.RANKL). By examination of Col1α1.CreER.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.
骨重建过程对正畸力的反应需要破骨细胞的活性，以使牙齿朝着施加力的方向移动。核因子-κB 受体激活剂配体（RANKL）对这个过程是必不可少的，尽管其在正畸力作用下的细胞来源尚未确定。正畸牙齿移动被认为是一种无菌性炎症过程，由包括 T 和 B 淋巴细胞在内的白细胞刺激，这些白细胞被认为刺激骨吸收。我们通过使用他莫昔芬诱导 RANKL 缺失来确定牙周韧带和骨衬细胞是否是 RANKL 的重要来源，其中 Cre 重组酶由 Col1α1 基因的 3.2kb 报告元件驱动（Col1α1.CreER.RANKL），并将结果与同窝对照（Col1α1.CreER.RANKL）进行比较。通过对 Col1α1.CreER.ROSA26 报告小鼠的检查，我们表明他莫昔芬诱导的 Cre 重组酶在牙周韧带和骨衬细胞中的组织特异性。令人惊讶的是，我们发现大多数正畸牙齿移动和破骨细胞形成都在实验小鼠中被阻断，这些小鼠的牙周韧带空间也减少了。因此，我们首次证明了牙周韧带和骨衬细胞产生的 RANKL 为正畸力作用下的牙齿移动和破骨细胞生成提供了主要驱动力。
