Department of Cariology and Endodontology, School of Dentistry, Lanzhou University, Lanzhou, China; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, California.
J Endod. 2019 Nov;45(11):1357-1364.e1. doi: 10.1016/j.joen.2019.07.014. Epub 2019 Sep 12.
Odontoblasts produce dentin throughout life and in response to trauma. The purpose of this study was to identify the roles of endogenous Wnt signaling in regulating the rate of dentin accumulation.
Histology, immunohistochemistry, vital dye labeling, and histomorphometric assays were used to quantify the rate of dentin accumulation as a function of age. Two strains of Wnt reporter mice were used to identify and follow the distribution and number of Wnt-responsive odontoblasts as a function of age. To show a causal relationship between dentin secretion and Wnt signaling, dentin accumulation was monitored in a strain of mice in which Wnt signaling was aberrantly elevated.
Dentin deposition occurs throughout life, but the rate of accumulation slows with age. This decline in dentin secretion correlates with a decrease in endogenous Wnt signaling. In a genetically modified strain of mice, instead of tubular dentin, aberrantly elevated Wnt signaling resulted in accumulation of reparative dentin or osteodentin secreted from predontoblasts.
Wnt signaling regulates dentin secretion by odontoblasts, and the formation of reparative or osteodentin is the direct consequence of elevated Wnt signaling. These preclinical data have therapeutic implications for the development of a biologically based pulp capping medicant.
成牙本质细胞在一生中都能产生牙本质,并能对创伤作出反应。本研究的目的是确定内源性 Wnt 信号在调节牙本质积累速度中的作用。
采用组织学、免疫组织化学、活体染料标记和组织形态计量学检测方法,定量测定牙本质积累速度随年龄的变化。使用两种 Wnt 报告基因小鼠品系来鉴定和追踪 Wnt 反应性成牙本质细胞的分布和数量随年龄的变化。为了显示牙本质分泌和 Wnt 信号之间的因果关系,在 Wnt 信号异常升高的小鼠品系中监测牙本质的积累情况。
牙本质沉积发生在整个生命过程中,但积累速度随年龄的增长而减慢。牙本质分泌的这种下降与内源性 Wnt 信号的减少相关。在一种基因修饰的小鼠品系中,异常升高的 Wnt 信号导致修复性牙本质或由前成牙本质细胞分泌的骨样牙本质的积累,而不是管状牙本质。
Wnt 信号通过成牙本质细胞调节牙本质分泌,而修复性或骨样牙本质的形成是 Wnt 信号升高的直接后果。这些临床前数据为开发基于生物学的牙髓盖髓药物提供了治疗意义。