Abstract:
The alveolar bone, with a high turnover rate, is the most actively-remodeling bone in the body. Orthodontic tooth movement (OTM) is a common artificial process of alveolar bone remodeling in response to mechanical force, but the underlying mechanism remains elusive. Previous studies have been unable to reveal the precise mechanism of bone remodeling in any time and space due to animal model-related restrictions. The signal transducer and activator of transcription 3 (STAT3) is important in bone metabolism, but its role in osteoblasts during OTM is unclear. To provide in vivo evidence that STAT3 participates in OTM at specific time points and in particular cells during OTM, we generated a tamoxifen-inducible osteoblast lineage-specific Stat3 knockout mouse model, applied orthodontic force, and analyzed the alveolar bone phenotype. Micro-computed tomography (Micro-CT) and stereo microscopy were used to access OTM distance. Histological analysis selected the area located within three roots of the first molar (M1) in the cross-section of the maxillary bone as the region of interest (ROI) to evaluate the metabolic activity of osteoblasts and osteoclasts, indicating the effect of orthodontic force on alveolar bone. In short, we provide a protocol for using inducible osteoblast lineage-specific Stat3 knockout mice to study bone remodeling under orthodontic force and describe methods for analyzing alveolar bone remodeling during OTM, thus shedding new light on skeletal mechanical biology.
摘要:
牙槽骨,换手率很高,是体内最积极重塑的骨骼。正畸牙齿移动(OTM)是响应机械力的牙槽骨重塑的常见人工过程,但是潜在的机制仍然难以捉摸。由于动物模型相关的限制,以往的研究一直无法揭示骨重建在任何时间和空间的精确机制。信号转导和转录激活因子3(STAT3)在骨代谢中具有重要作用,但其在OTM期间成骨细胞中的作用尚不清楚。为了提供体内证据,STAT3在特定时间点参与OTM,特别是OTM期间的细胞,我们建立了一个他莫昔芬诱导的成骨细胞谱系特异性Stat3基因敲除小鼠模型,施加正畸力,并分析牙槽骨表型。微计算机断层扫描(Micro-CT)和立体显微镜用于访问OTM距离。组织学分析选择位于上颌骨横切面的第一磨牙(M1)三根内的区域作为目的区域(ROI),评价成骨细胞和破骨细胞的代谢活性,说明正畸力对牙槽骨的影响。总之,我们提供了使用诱导型成骨细胞谱系特异性Stat3敲除小鼠研究正畸力下的骨重建的方案,并描述了在OTM期间分析牙槽骨重建的方法,从而为骨骼机械生物学提供了新的思路。