Clinical Oral Investigations

, Volume 22, Issue 7, pp 2559–2566 | Cite as

Expression and localization of CRAMP in rat tooth germ and during reparative dentin formation

  • Kanji HoribeEmail author
  • Akihiro Hosoya
  • Toru Hiraga
  • Hiroaki Nakamura
Original Article



Cathelicidin-related antimicrobial peptide (CRAMP) is an antimicrobial peptide in mice and rats homologous to LL-37 in humans. In addition to its antibacterial activity, CRAMP has various physiological functions by binding to formyl peptide receptor 2 (FPR2). However, the role of these peptides in teeth is unknown. Therefore, we investigated the role of CRAMP and FPR2 in tooth development, reparative dentin formation, and defense response.

Material and methods

First, we examined the localization of CRAMP and FPR2 during tooth development by immunohistochemical analysis. Next, we investigated the localization of CRAMP, FPR2, and CD68-positive macrophages by immunohistochemical analysis during pulp inflammation and reparative dentin formation after cavity preparation. Finally, we analyzed the effect of lipopolysaccharide (LPS) on the expression of CRAMP and FPR2 in dental pulp cells by real-time reverse transcription PCR.


At the late bell stage in tooth development, CRAMP was detected in odontoblasts, and FPR2 was observed in the sub-odontoblastic layer. In mature teeth, CRAMP was not detected, but FPR2 continued to be localized in the sub-odontoblastic layer. After cavity preparation, CRAMP-positive cells and macrophages were found in dental pulp tissues below the cavity at an early stage of repair. At subsequent stages of reparative dentin formation, CRAMP was observed in odontoblast-like cells that contacted reparative dentin. FPR2 immunoreactivity was also detected in odontoblast-like cells and neighboring cells. LPS stimulated the expression of CRAMP mRNA in dental pulp cells in vitro.


Localization of CRAMP and its receptor FPR2-positive cells were observed during physiological and reparative dentin formation.

Clinical relevance

CRAMP/LL-37 has a possibility that induce reparative dentin formation.


Antimicrobial peptide Tooth development Cavity preparation Odontoblast Reparative dentin 



We express our sincere thanks to Dr. Takahashi of the Institute for Oral Science, Matsumoto Dental University for helpful discussions and encouragement.


This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP26893301.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

All experiments were conducted in accordance with the guidelines for studies with laboratory animals of the Matsumoto Dental University Experimental Animal Committee.

Informed consent

For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Oral HistologyMatsumoto Dental UniversityNaganoJapan
  2. 2.Department of Histology, School of DentistryHealth Sciences University of HokkaidoHokkaidoJapan

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