The Essential Role of Proteoglycans and Glycosaminoglycans in Odontogenesis.

Journal of dental research Pub Date : 2024-04-01 Epub Date: 2024-02-26 DOI:10.1177/00220345231224228
J Chen, T Sun, B Lin, B Wu, J Wu
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Abstract

Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling regulatory networks, but the regulatory roles of extracellular networks have only been revealed recently. Proteoglycans, which are essential components of the extracellular matrix (ECM) and pivotal signaling molecules, are extensively involved in the process of odontogenesis. Proteoglycans are composed of core proteins and covalently attached glycosaminoglycan chains (GAGs). The core proteins exhibit spatiotemporal expression patterns during odontogenesis and are pivotal for dental tissue formation and periodontium development. Knockout of core protein genes Biglycan, Decorin, Perlecan, and Fibromodulin has been shown to result in structural defects in enamel and dentin mineralization. They are also closely involved in the development and homeostasis of periodontium by regulating signaling transduction. As the functional component of proteoglycans, GAGs are negatively charged unbranched polysaccharides that consist of repeating disaccharides with various sulfation groups; they provide binding sites for cytokines and growth factors in regulating various cellular processes. In mice, GAG deficiency in dental epithelium leads to the reinitiation of tooth germ development and the formation of supernumerary incisors. Furthermore, GAGs are critical for the differentiation of dental stem cells. Inhibition of GAGs assembly hinders the differentiation of ameloblasts and odontoblasts. In summary, core proteins and GAGs are expressed distinctly and exert different functions at various stages of odontogenesis. Given their unique contributions in odontogenesis, this review summarizes the roles of proteoglycans and GAGs throughout the process of odontogenesis to provide a comprehensive understanding of tooth development.

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蛋白聚糖和糖胺聚糖在牙齿生成过程中的重要作用
牙齿的发育和再生是通过复杂的信号网络调控的。以往的研究侧重于细胞内信号调控网络的探索,但细胞外网络的调控作用直到最近才被揭示出来。蛋白聚糖是细胞外基质(ECM)的重要组成部分,也是关键的信号分子,广泛参与牙体发生过程。蛋白多糖由核心蛋白和共价连接的糖胺聚糖链(GAGs)组成。核心蛋白在牙体发生过程中呈现时空表达模式,是牙组织形成和牙周发育的关键。研究表明,敲除核心蛋白基因 Biglycan、Decorin、Perlecan 和 Fibromodulin 会导致釉质和牙本质矿化的结构缺陷。它们还通过调节信号转导密切参与牙周的发育和平衡。作为蛋白多糖的功能成分,GAGs 是一种带负电荷的无支链多糖,由带有不同硫酸化基团的重复二糖组成;它们为细胞因子和生长因子提供结合位点,以调节各种细胞过程。在小鼠中,牙上皮细胞缺乏 GAG 会导致牙齿胚芽发育的重启和超常门齿的形成。此外,GAGs 对牙齿干细胞的分化至关重要。抑制 GAGs 的组装会阻碍成釉细胞和牙本质细胞的分化。总之,核心蛋白和GAGs在牙体发生的不同阶段表达不同,发挥不同的功能。鉴于它们在牙体发生过程中的独特贡献,本综述总结了蛋白多糖和 GAGs 在整个牙体发生过程中的作用,以提供对牙齿发育的全面认识。
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