Kero Darko, Bilandzija Tanja Simic, Arapovic Lidija Lasic, Vukojevic Katarina, Saraga-Babic Mirna
Department of Dental Morphology and Anthropology, Study Program of Dental Medicine, School of Medicine, University of Split, Split, Croatia.
Department of Maxillofacial Surgery, University Clinical Hospital Mostar, Mostar, Bosnia and Herzegovina.
Front Physiol. 2018 Jun 14;9:732. doi: 10.3389/fphys.2018.00732. eCollection 2018.
Syndecans belong to a four-member family of cell surface heparan sulfate proteoglycans (HSPGs) abundantly present in various tissues. They are primarily recognized as extracellular matrix (ECM) receptors able to bind various ECM components and form gradients of morphogens and growth factors. Syndecans are composed of core protein with distinctive cytoplasmic, transmembrane, and extracellular domains to which several HS glycosaminoglycan (GAG) chains are covalently attached. In development of composite organs, such as teeth, expression patterns of syndecans display temporo-spatial shifts between epithelial and mesenchymal tissue compartments. Along with diverse functional properties of syndecans and generally large number of their interactors due to HS GAG chain content, this suggests possible involvement of syndecans in modulation of epithelial-to-mesenchymal crosstalk. Functional versatility of syndecans greatly depends upon the biochemical properties of attached HS GAG chains. These are specifically determined during the HS biosynthesis by the combinatorial action of glycosyl-transferases (Exts/EXTs) and bi-functional sulfotransferases (Ndsts/NDSTs), as well as by post-biosynthetic enzymatic cleavage of HS by the only active endoglucuronidase in mammals, heparanase 1 (Hpse1/HPSE1). Matching the essential requirement for HS during organogenesis, null-mutant animals for genes encoding these enzymes display severe developmental anomalies of mineralized tissues (including teeth) with embryonic or perinatal lethality. In this study, we analyzed expression of syndecan HSPGs (syndecans 1, 2, and 4), enzymes involved in HS biosynthesis (EXT1, NDST1, NDST2) and HS cleavage (HPSE1) in human tooth germs during the early stages of odontogenesis. All of the investigated factors displayed temporo-spatial differences in expression patterns, and some of them showed distinctive asymmetries of expression domains. Our findings suggest that these factors might be differentially involved in cellular processes which take place during the early odontogenic sequence in humans.
Syndecans属于一个由四个成员组成的细胞表面硫酸乙酰肝素蛋白聚糖（HSPG）家族，在各种组织中大量存在。它们主要被认为是细胞外基质（ECM）受体，能够结合各种ECM成分，并形成形态发生素和生长因子的梯度。Syndecans由具有独特细胞质、跨膜和细胞外结构域的核心蛋白组成，几条硫酸乙酰肝素（HS）糖胺聚糖（GAG）链共价连接到该核心蛋白上。在复合器官（如牙齿）的发育过程中，Syndecans的表达模式在上皮和间充质组织区室之间表现出时空变化。由于HS GAG链的含量，Syndecans具有多种功能特性，并且其相互作用分子的数量通常很多，这表明Syndecans可能参与上皮-间充质相互作用的调节。Syndecans的功能多样性在很大程度上取决于所连接的HS GAG链的生化特性。这些特性在HS生物合成过程中由糖基转移酶（Exts/EXTs）和双功能磺基转移酶（Ndsts/NDSTs）的组合作用特异性决定，以及由哺乳动物中唯一的活性内切葡糖醛酸酶乙酰肝素酶1（Hpse1/HPSE1）对HS进行生物合成后酶切决定。符合器官发生过程中对HS的基本要求，编码这些酶的基因的无效突变动物表现出矿化组织（包括牙齿）的严重发育异常，并伴有胚胎或围产期致死率。在本研究中，我们分析了人牙胚在牙发生早期阶段Syndecan HSPG（Syndecan 1、2和4）、参与HS生物合成的酶（EXT1、NDST1、NDST2）和HS裂解酶（HPSE1）的表达。所有研究的因子在表达模式上都表现出时空差异，其中一些因子表现出独特的表达域不对称性。我们的研究结果表明，这些因子可能在人类早期牙发生序列中发生的细胞过程中发挥不同的作用。
