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利用诱导性成骨细胞谱系特异性 Stat3 敲除小鼠研究正畸牙齿移动过程中的牙槽骨重塑。

Using Inducible Osteoblastic Lineage-Specific Stat3 Knockout Mice to Study Alveolar Bone Remodeling During Orthodontic Tooth Movement.

机构信息

Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology.

Shanghai Starriver Bilingual School.

出版信息

J Vis Exp. 2023 Jul 21(197). doi: 10.3791/65613.

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

牙槽骨具有较高的周转率,是体内最活跃的重塑骨骼。正畸牙齿移动(OTM)是一种常见的人工牙槽骨重塑过程,以应对机械力,但潜在机制仍不清楚。由于动物模型相关限制,以前的研究无法在任何时间和空间揭示骨骼重塑的确切机制。信号转导子和转录激活子 3(STAT3)在骨骼代谢中很重要,但它在 OTM 期间成骨细胞中的作用尚不清楚。为了提供体内证据,证明 STAT3 在 OTM 期间特定时间点和特定细胞中参与 OTM,我们生成了一种他莫昔芬诱导的成骨细胞谱系特异性 Stat3 敲除小鼠模型,施加正畸力,并分析了牙槽骨表型。微计算机断层扫描(Micro-CT)和立体显微镜用于评估 OTM 距离。组织学分析选择上颌骨横截面中第一磨牙(M1)的三个根内的区域作为感兴趣区域(ROI),以评估成骨细胞和破骨细胞的代谢活性,表明正畸力对牙槽骨的影响。简而言之,我们提供了一种使用诱导性成骨细胞谱系特异性 Stat3 敲除小鼠来研究正畸力下骨骼重塑的方案,并描述了分析 OTM 期间牙槽骨重塑的方法,从而为骨骼机械生物学提供了新的视角。

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