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.

中文翻译：

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蛋白聚糖和糖胺聚糖在牙发育中的重要作用

牙齿的发育和再生通过复杂的信号网络进行调节。先前的研究主要集中在细胞内信号调节网络的探索上，但细胞外网络的调节作用最近才被揭示。蛋白多糖是细胞外基质（ECM）的重要组成部分和关键信号分子，广泛参与牙发育过程。蛋白聚糖由核心蛋白和共价连接的糖胺聚糖链 (GAG) 组成。核心蛋白在牙发生过程中表现出时空表达模式，对于牙组织形成和牙周发育至关重要。敲除核心蛋白基因 Biglycan、Decorin、Perlecan 和 Fibromodulin 已被证明会导致牙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组织的发育和稳态。作为蛋白聚糖的功能成分，GAG 是带负电荷的无支链多糖，由带有各种硫酸化基团的重复二糖组成；它们为调节各种细胞过程的细胞因子和生长因子提供结合位点。在小鼠中，牙上皮中的 GAG 缺陷会导致牙胚发育重新启动和多生门牙的形成。此外，GAG 对于牙齿干细胞的分化至关重要。抑制 GAG 组装会阻碍成釉细胞和成牙本质细胞的分化。综上所述，核心蛋白和GAG在牙发生的不同阶段表达不同，发挥不同的功能。鉴于蛋白聚糖和 GAG 在牙发育过程中的独特贡献，本文总结了蛋白多糖和 GAG 在整个牙发育过程中的作用，以提供对牙齿发育的全面了解。