Department of Oral and Maxillofacial Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Histochem Cell Biol. 2010 Dec;134(6):603-14. doi: 10.1007/s00418-010-0756-0. Epub 2010 Nov 11.
Maspin is a 42 kDa serine protease inhibitor that possesses tumor suppressive and anti-angiogenic activities. Despite of a huge amount of data concerning the expression pattern of maspin in various tissues and its relevance to the biological properties of a variety of human cancer cells, little is known on the maspin expression in skeletal and tooth tissues. Recently, we reported that maspin may play an important role in extracellular matrix formation in bone by enhancing the accumulation of latent TGF-β in the extracellular matrix. This study was performed to elucidate the possible role of maspin in tooth development. First, an immunohistochemical analysis for human tooth germs at the late bell stage showed the expression of maspin by active ameloblasts and odontoblasts that were forming enamel and dentin, respectively. During rat tooth development, maspin expression was observed for the first time in inner and outer enamel epithelial cells and dental papilla cells at early bell stage. The neutralizing anti-maspin antibody inhibited the proper dental tissue formation in organ cultures of mandibular first molars obtained from 21-day-old rat embryos. In addition, the proliferation of HAT-7 cells, a rat odontogenic epithelial cell line, and human dental papilla cells were suppressed in a dose-dependent manner with anti-maspin antibody. Moreover, RT-PCR analysis showed that the expression of mRNA for tooth-related genes including dentin matrix protein 1, dentin sialophosphoprotein and osteopontin in human dental papilla cells was inhibited when treated with anti-maspin antibody. These findings suggest that maspin expressed in ameloblasts and odontoblasts plays an important physiological role in tooth development through the regulation of matrix formation in dental tissues.
Maspin 是一种 42kDa 的丝氨酸蛋白酶抑制剂，具有肿瘤抑制和抗血管生成活性。尽管有大量关于 maspin 在各种组织中的表达模式及其与多种人类癌细胞生物学特性的相关性的数据，但对于骨骼和牙齿组织中的 maspin 表达知之甚少。最近，我们报道了 maspin 可能通过增强细胞外基质中潜伏 TGF-β的积累在骨细胞外基质形成中发挥重要作用。本研究旨在阐明 maspin 在牙齿发育中的可能作用。首先，对晚期钟状期人类牙胚进行免疫组织化学分析显示，maspin 由正在形成釉质和牙本质的活性成釉细胞和成牙本质细胞表达。在大鼠牙齿发育过程中，maspin 表达首次在早期钟状期的内釉上皮细胞和牙髓细胞中观察到。中和抗 maspin 抗体抑制了从小鼠胚胎 21 天获得的下颌第一磨牙下颌第一磨牙器官培养中正常牙齿组织的形成。此外，抗 maspin 抗体以剂量依赖的方式抑制 HAT-7 细胞（大鼠牙源性上皮细胞系）和人牙髓细胞的增殖。此外，RT-PCR 分析显示，用抗 maspin 抗体处理可抑制人牙髓细胞中牙相关基因包括牙本质基质蛋白 1、牙本质涎磷蛋白和骨桥蛋白的 mRNA 表达。这些发现表明，成釉细胞和成牙本质细胞中表达的 maspin 通过调节牙齿组织中基质的形成，在牙齿发育中发挥重要的生理作用。
