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Differential expression of transforming growth factor-beta1, connective tissue growth factor, phosphorylated-SMAD2/3 and phosphorylated-ERK1/2 during mouse tooth development

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Abstract

Connective tissue growth factor (CTGF) is a downstream mediator of transforming growth factor-beta 1 (TGF-β1) and TGF-β1-induced CTGF expression is regulated through SMAD and mitogen-activated protein kinase (MAPK) signaling pathways. The fine modulation of TGF-β1 signaling is very important to the process of tooth development. However, little is known about the localization of CTGF, MAPK and SMAD in the context of TGF-β1 signaling during odontogenesis. Hence, we aimed to investigate the expression of TGF-β1, CTGF, phosphorylated-SMAD2/3 (p-SMAD2/3) and phosphorylated-ERK1/2 (p-ERK1/2). ICR mice heads of embryonic (E) day 13.5, E14.5, E16.5, postnatal (PN) day 0.5 and PN3.5 were processed for immunohistochemistry. Results revealed that at E13.5, TGF-β1 and CTGF were strongly expressed in dental epithelium (DE) and dental mesenchyme (DM), while p-SMAD2/3 was intensely expressed in the internal side of DE. p-ERK1/2 was not present in DE or DM. At E14.5 and E16.5, strong staining for TGF-β1 and CTGF was detected in enamel knot (EK) and dental papilla (DPL). DPL was intensely stained for p-ERK1/2 but negatively stained for p-SMAD2/3. There was no staining for p-SMAD2/3 and p-ERK1/2 in EK. At PN0.5 and PN3.5, moderate to intense staining for TGF-β1 and CTGF was evident in preameloblasts (PA), secretary ameloblasts (SA) and dental pulp (DP). p-SMAD2/3 was strongly expressed in SA and DP but sparsely localized in PA. p-ERK1/2 was intensely expressed in DP, although negative staining was observed in PA and SA. These data demonstrate that TGF-β1 and CTGF show an identical expression pattern, while p-SMAD2/3 and p-ERK1/2 exhibit differential expression, and indicate that p-SMAD2/3 and p-ERK1/2 might play a regulatory role in TGF-β1 induced CTGF expression during tooth development.

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Acknowledgements

This study was supported by the Zhejiang Province Natural Science Foundation (Grant No: LY16H140005) and Wenzhou Science and Technology Planning Project (Grant No: Y20150077).

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Authors and Affiliations

  1. The Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China

    Shubo Li & Yihuai Pan

  2. Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, 113 West Xueyuan Road, Wenzhou, 325027, Zhejiang, People’s Republic of China

    Yihuai Pan

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  1. Shubo Li
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Li, S., Pan, Y. Differential expression of transforming growth factor-beta1, connective tissue growth factor, phosphorylated-SMAD2/3 and phosphorylated-ERK1/2 during mouse tooth development. J Mol Hist 48, 347–355 (2017). https://doi.org/10.1007/s10735-017-9733-4

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  • DOI: https://doi.org/10.1007/s10735-017-9733-4

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