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Regulatory role of insulin-like growth factor-binding proteins in odontogenic mineralization in rats

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Abstract

Much information is currently available for molecules in early odontogenesis, but there is limited knowledge regarding terminal cytodifferentiation of ameloblasts and odontoblasts for the determination of normal crown morphology. The present differential display PCR (DD-PCR) revealed that insulin-like growth factor-binding protein 5 (IGFBP5) was differentially expressed in molar tooth germs between the cap (before crown mineralization) and root formation (after crown mineralization) stages. Real-time PCR confirmed that the expression levels of IGFBP1–4 were not significantly changed but those of IGFBP5–7 were upregulated in a time-dependent manner. Immunoreactivities for IGFBP5–7 were hardly seen in molar germs at the cap/early bell stage and protective-stage ameloblasts at the root formation stage. However, the reactivity was strong in odontoblasts and maturation-stage ameloblasts, which are morphologically and functionally characterized by wide intercellular space and active enamel matrix mineralization. The localization of each IGFBP was temporospatial. IGFBP5 was localized in the nuclei of fully differentiated odontoblasts and ameloblasts, while IGFBP6 was localized in the apical cytoplasm of ameloblasts and odontoblasts with dentinal tubules, and IGFBP7 was mainly found in the whole cytoplasm of odontoblasts and the intercellular space of ameloblasts. IGFBP silencing using specific siRNAs upregulated representative genes for dentinogenesis and amelogenesis, such as DMP1 and amelogenin, respectively, and augmented the differentiation media-induced mineralization, which was confirmed by alizarin red s and alkaline phosphatase staining. These results suggest that IGFBP5–7 may play independent and redundant regulatory roles in late-stage odontogenesis by modulating the functional differentiation of ameloblasts and odontoblasts.

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Funding

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. 2019R1A5A2027521) and (No. 2019R1A2C1003520). The authors report no conflicts of interest related to this study.

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  1. Jung-Sun Moon and Yoo-Sung Nam have contribute to this work equally.

Authors and Affiliations

  1. Department of Oral Anatomy, Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea

    Jung-Sun Moon, Yoo-Sung Nam, Jee-Hae Kang, Dong-Wook Yang, Dae-Yoon Kim, Su-Young Lee, Hyun-Mi Ko, Min-Seok Kim & Sun-Hun Kim

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  1. Jung-Sun Moon
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Contributions

JSM and YSN contributed to conception, data acquisition, analysis and interpretation; JHK, SYL, and DYK drafted and revised the manuscript; DWY, HMK, and MSK contributed to conception and design; SHK contributed to design and data interpretation and critically revised the manuscript.

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Correspondence to Sun-Hun Kim.

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Moon, JS., Nam, YS., Kang, JH. et al. Regulatory role of insulin-like growth factor-binding proteins in odontogenic mineralization in rats. J Mol Histol 52, 63–75 (2021). https://doi.org/10.1007/s10735-020-09923-3

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