Tubular Dentin Regeneration Using a CPNE7-Derived Functional Peptide
Yoon Seon Lee,
Yeoung-Hyun Park,
Dong-Seol Lee,
You-Mi Seo,
Ji-Hyun Lee,
Joo-Hwang Park,
Han-Wool Choung,
So-Hyun Park,
Won Jun Shon,
Joo-Cheol Park
Affiliations
Yoon Seon Lee
Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology—Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 08826, Korea
Yeoung-Hyun Park
Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology—Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 08826, Korea
Dong-Seol Lee
Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology—Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 08826, Korea
You-Mi Seo
Regenerative Dental Medicine R and D Center, HysensBio Co., Ltd., Seoul 03080, Korea
Ji-Hyun Lee
Regenerative Dental Medicine R and D Center, HysensBio Co., Ltd., Seoul 03080, Korea
Joo-Hwang Park
Regenerative Dental Medicine R and D Center, HysensBio Co., Ltd., Seoul 03080, Korea
Han-Wool Choung
Department of Oral and Maxillofacial Surgery, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Korea
So-Hyun Park
Department of Conservative Dentistry, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Korea
Won Jun Shon
Department of Conservative Dentistry, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Korea
Joo-Cheol Park
Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology—Developmental Biology, School of Dentistry and Dental Research Institute, BK 21, Seoul National University, Seoul 08826, Korea
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.
