Aizawa Chisato, Saito Kotaro, Ohshima Hayato
Faculty of Dentistry, Niigata University, Niigata, Japan.
Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Oral Biosci. 2019 Sep;61(3):157-162. doi: 10.1016/j.job.2019.07.001. Epub 2019 Aug 7.
Although intracellular signaling pathways of insulin-like growth factor I (IGF-I) related to the proliferation of dental pulp cells have been investigated, the switching mechanism from cell proliferation to differentiation during odontogenesis remains elusive. This study aimed to elucidate the role of IGF binding protein (IGFBP) 3 and 5 in regulation of IGF-I during odontoblast differentiation in mouse incisors.
The detailed expression patterns of IGF-I, IGF-I receptor (IGF-IR), IGFBP3, and IGFBP5 together with that of an odontoblast differentiation marker, nestin, were examined by immunohistochemistry and/or in situ hybridization using paraffinized sections of TetOP-H2B-GFP mouse incisors at postnatal 4 weeks.
Undifferentiated dental papilla cells and preodontoblasts (preOB) showed intense IGF-I- and IGF-IRα-positive reactions, and the expression was observed in differentiated odontoblasts, such as immature odontoblasts (iOB) and mature odontoblasts (mOB). IGFBP3/Igfbp3 was transiently expressed in preOB and early iOB, and the intensity of expression gradually reduced with the progression of odontoblast differentiation. In contrast, immunohistochemical analysis for IGFBP5 identified a positive reaction in the undifferentiated dental papilla cells and differentiated odontoblasts, and the expression of Igfbp5 was reduced in the differentiated odontoblasts.
The present study demonstrated the expression patterns of IGF-I, IGF-IR, IGFBP3, and IGFBP5 during odontoblast differentiation in mouse incisors. These results suggested that IGFBP3 regulates the transition from the proliferative to differentiation stage by inhibiting the action of IGF-I on the proliferation of dental papilla cells, and that IGFBP5 plays an important role in the maintenance of the differentiated odontoblasts during tooth development.
尽管已经研究了胰岛素样生长因子I（IGF-I）与牙髓细胞增殖相关的细胞内信号通路，但牙发生过程中从细胞增殖向分化的转换机制仍不清楚。本研究旨在阐明IGF结合蛋白（IGFBP）3和5在小鼠切牙成牙本质细胞分化过程中对IGF-I的调节作用。
使用出生后4周的TetOP-H2B-GFP小鼠切牙的石蜡切片，通过免疫组织化学和/或原位杂交检查IGF-I、IGF-I受体（IGF-IR）、IGFBP3和IGFBP5以及成牙本质细胞分化标志物巢蛋白的详细表达模式。
未分化的牙乳头细胞和前成牙本质细胞（preOB）显示出强烈的IGF-I和IGF-IRα阳性反应，并且在分化的成牙本质细胞中观察到表达，如未成熟成牙本质细胞（iOB）和成熟成牙本质细胞（mOB）。IGFBP3/Igfbp3在preOB和早期iOB中短暂表达，并且随着成牙本质细胞分化的进展，表达强度逐渐降低。相反，IGFBP5的免疫组织化学分析在未分化的牙乳头细胞和分化的成牙本质细胞中鉴定出阳性反应，并且Igfbp5的表达在分化的成牙本质细胞中降低。
本研究证明了IGF-I、IGF-IR、IGFBP3和IGFBP5在小鼠切牙成牙本质细胞分化过程中的表达模式。这些结果表明，IGFBP3通过抑制IGF-I对牙乳头细胞增殖的作用来调节从增殖阶段到分化阶段的转变，并且IGFBP5在牙齿发育过程中维持分化的成牙本质细胞中起重要作用。
