Although insulin-like growth factor binding protein 5 (IGFBP5) may play a crucial role in activating the functions of periodontal and bone marrow stem cells, the factors responsible for regulating the maintenance of dental pulp stem cells (DPSCs) remain to be clarified. This study aimed to elucidate the role of IGFBP5 in maintaining pulpal homeostasis during tooth development and pulpal healing after tooth injury in doxycycline-inducible TetOP-histone 2B (H2B)-green fluorescent protein (GFP) transgenic mice (GFP expression was induced at E14.5 or E15.5) by using TUNEL assay, RT-PCR, in situ hybridization for Igfbp5, and immunohistochemistry for IGFBP5, Nestin, and GFP. To observe the pulpal response to exogenous stimuli, the roots of the maxillary first molars were resected, and the coronal portion was autografted into the sublingual region. Intense IGFBP5/Igfbp5 expression was observed in cells from the center of the pulp tissue and the subodontoblastic layer in developing teeth during postnatal Week 4. Intense H2B-GFP-expressing label-retaining cells (LRCs) were localized in the subodontoblastic layer in addition to the center of the pulp tissue, suggesting that slowly dividing cell populations reside in these areas. During postoperative days 3–7, the LRCs were maintained in the dental pulp, showed an IGFBP5-positve reaction in their nuclei, and lacked a TUNEL-positive reaction. In situ hybridization and RT-PCR analyses confirmed the expression of Igfbp5 in the dental pulp. These findings suggest that IGFBP5 play a pivotal role in regulating the survival and apoptosis of DPSCs during both tooth development and pulpal healing following tooth injury.

尽管胰岛素样生长因子结合蛋白5（IGFBP5）可能在激活牙周和骨髓干细胞的功能中起关键作用，但负责调节牙髓干细胞（DPSCs）维持的因素仍有待阐明。这项研究旨在阐明在强力霉素诱导的TetOP-组蛋白2B（H2B）-绿色荧光蛋白（GFP）转基因小鼠中，IGFBP5在维持牙齿发育和牙髓损伤后牙髓稳态中的作用（在E14诱导GFP表达。 5或E15.5），使用TUNEL分析，RT-PCR，Igfbp5原位杂交，和IGFBP5，Nestin和GFP的免疫组化。为了观察牙髓对外源性刺激的反应，切除上颌第一磨牙的根，并将冠状部分自体移植到舌下区域。出生后第4周，在发育中牙齿的牙髓组织中心和牙釉质下层中的细胞中观察到了强烈的IGFBP5 / Igfbp5表达。除了H2B-GFP表达标签保持细胞（LRC）外，还存在于牙本质成骨层中在牙髓组织的中心，这表明缓慢分裂的细胞群位于这些区域。术后3-7天，LRC保留在牙髓中，在其细胞核中显示出IGFBP5阳性反应，而缺乏TUNEL阳性反应。原位杂交和RT-PCR分析证实了Igfbp5在牙髓中的表达。这些发现表明，IGFBP5在调节牙齿损伤后牙发育和牙髓愈合过程中DPSC的存活和凋亡中起着关键作用。