Tubular Dentin Regeneration Using a CPNE7-Derived Functional Peptide.

Yoon Seon Lee,Joo-Cheol Park,Yeoung-Hyun Park,So-Hyun Park,You-Mi Seo,Won Jun Shon,Dong-Seol Lee,Han-Wool Choung,Ji-Hyun Lee,Joo-Hwang Park

doi:10.3390/ma13204618

Abstract

We aim to examine the effects of a newly developed peptide derived from CPNE7 (Cpne7-DP) in tertiary dentin formation and peritubular space occlusion, and comprehensively evaluate its potential as a bioactive therapeutic agent. Human dental pulp cells (HDPCs) and a mouse pre-odontoblast cell line, MDPC-23, were chosen for in vitro studies to characterize lineage-specific cell responses after Cpne7-DP treatment. Whether Cpne7-DP reproduces the dentin regenerative potential of CPNE7 was tested using a beagle dog model by generating dentinal defects of various degrees in vivo. Peritubular space occlusion was further examined by scanning electron microscopy and microleakage test, while overall mineralization capacity of Cpne7-DP was tested ex vivo. CPNE7 promotes tubular dentin formation under both shallow and deep dentinal defects, and the functional peptide Cpne7-DP induces odontoblast-like differentiation in vitro, mineralization ex vivo, and tubular dentin formation in in vivo beagle dog dentin exposure and pulp exposure models. Moreover, Cpne7-DP leads to peritubular space occlusion and maintains stability under different conditions. We show that CPNE7 and its derivative functional peptide Cpne7-DP promotes dentin regeneration in dentinal defects of various degrees and that the regenerated hard tissue demonstrates the characteristics of true dentin. Limitations of the current dental materials including post-operative hypersensitivity make biological repair of dentin a field of growing interest. Here, we suggest that the dual functions of Cpne7-DP in tubular dentin formation and peritubular space occlusion are promising for the treatment of dentinal loss and sensitivity.

Highlights

Loss of tooth dentin generates unpleasant pain but leads to the weakening of whole tooth stability due to reduced dentin thickness
To assess the effects of recombinant Copine 7 (CPNE7) in varying extents of dentinal defects, both shallow and deep cavities were artificially generated in beagle dog premolars (Figure 1a) and divided into two groups each (n = 6 for all groups): glass ionomer (GI), cement filling only (Control), and GI
We further evaluated the role of Cpne7-DP by transplanting human dental pulp cells (hDPCs) into the subcutaneous tissues of immunocompromised mice using hydroxyapatite/tricalcium phosphate (HA/TCP) under three different conditions: hDPCs only (Control), hDPCs treated with Cpne7-DP, and hDPCs treated with recombinant bone morphogenetic protein 2

Summary

Introduction

Loss of tooth dentin generates unpleasant pain but leads to the weakening of whole tooth stability due to reduced dentin thickness. Dental caries is the most prevalent chronic disease in both children and adults, affecting more than 5 billion people worldwide. Dental caries is caused by bacterial infection and resulting acidic byproducts that demineralize the tooth. Exposed dentinal tubules in dental caries serve as a route. A healthy tooth is composed of nearly 70% dentin enclosing the entire dental pulp, which is a pool of diverse stem cells [4]. Loss of tooth dentin generates unpleasant sensitivity but leads to the weakening of whole tooth stability due to reduced dentin thickness. Most of the previously reported reparative tertiary dentin shows features of osteodentin, which is composed of bone-like structures with osteocyte-resembling cells entrapped in lacunae-like spaces [5]

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