Tubular Dentin Regeneration Using a CPNE7-Derived Functional Peptide

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

doi:10.3390/ma13204618

Cited by 25 publications

(22 citation statements)

References 40 publications

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“…All experiments using beagles were conducted under the guidelines provided by the Institutional Animal Care and Use Committee of Seoul National University (SNU-171020-5-2). The indirect pulp capping was performed as described previously ( Lee et al, 2020 ). Three beagle dogs (aged 1-2 y) were examined throughout the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…This secreted factor from the pre-ameloblasts, binds to nucleolin on the cell surface of pre-odontoblasts and translocates to the nucleus, where it regulates dentin sialophosphoprotein ( Dspp ) expression ( Seo et al, 2017 ; Park et al, 2019 ). Of the numerous odontoblast differentiation-promoting factors reported so far, non-collagenous dentin matrix proteins ( Duque et al, 2006 ; Kim, 2017 ) and CPNE7 ( Choung et al, 2016 ; Lee et al, 2020 ) have been shown to form the physiological tubular dentin that contains the dentinal tubules that hold the odontoblast processes. However, the precise mechanism of CPNE7-mediated physiologic tubular dentin regeneration in adult dentin has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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CPNE7-Induced Autophagy Restores the Physiological Function of Mature Odontoblasts

Park¹,

Son²,

Seo³

et al. 2021

Front. Cell Dev. Biol.

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Dentin, which composes most of the tooth structure, is formed by odontoblasts, long-lived post-mitotic cells maintained throughout the entire life of the tooth. In mature odontoblasts, however, cellular activity is significantly weakened. Therefore, it is important to augment the cellular activity of mature odontoblasts to regenerate physiological dentin; however, no molecule regulating the cellular activity of mature odontoblasts has yet been identified. Here, we suggest that copine-7 (CPNE7) can reactivate the lost functions of mature odontoblasts by inducing autophagy. CPNE7 was observed to elevate the expression of microtubule-associated protein light chain 3-II (LC3-II), an autophagy marker, and autophagosome formation in the pre-odontoblast and mature odontoblast stages of human dental pulp cells. CPNE7-induced autophagy upregulated DSP and DMP-1, odontoblast differentiation and mineralization markers, and augmented dentin formation in mature odontoblasts. Furthermore, CPNE7 also upregulated NESTIN and TAU, which are expressed in the physiological odontoblast process, and stimulated the elongation of the odontoblast process by inducing autophagy. Moreover, lipofuscin, which progressively accumulates in long-lived post-mitotic cells and hinders their proper functions, was observed to be removed in recombinant CPNE7-treated mature odontoblasts. Thus, CPNE7-induced autophagy reactivated the function of mature odontoblasts and promoted the formation of physiological dentin in vivo. On the other hand, the well-known autophagy inducer, rapamycin, promoted odontoblast differentiation in pre-odontoblasts but did not properly reactivate the function of mature odontoblasts. These findings provide evidence that CPNE7 functionally reactivates mature odontoblasts and introduce its potential for dentinal loss-targeted clinical applications.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CPNE7-Induced Autophagy Restores the Physiological Function of Mature Odontoblasts

Park¹,

Son²,

Seo³

et al. 2021

Front. Cell Dev. Biol.

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“…Another peptide is Cpne7-DP, which can be placed on 0.5% fibrin gel and then transplanted subcutaneously into immunocompromised mice. Twelve weeks after the transplantation, the Cpne7-DP treatment group showed the formation of dentin-pulp-like tissue with cells inserting long cellular processes into the tubule-like structure formed within newly mineralized tissue (Lee et al, 2020).…”

Section: Peptides For Dentin-pulp Complex Regenerationmentioning

confidence: 98%

“…In vitro analyses included the effects of the addition of the recombinant proteins or peptides on cell proliferation, differentiation, and Proliferation and differentiation of dental pulp cells Huang et al (2012) adhesion of postnatal human dental pulp cells (DPCs) In vivo analyses were completed following the insertion of agarose beads containing LRAP or LRAP 8, 9 into exposed cavity preparations of rat molars. After 8, 15, or 30 days' exposure, the pulp tissues were analyzed for changes in histomorphometry and cell proliferation by PCNA staining Copine 7 derived peptide (Cpne7-DP) (KYKQKRRSYK) 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 Promotes dentin regeneration, differentiation cellular Lee et al (2020) In vivo Cpne7-DP was tested using a beagle dog model by generating dentinal defects of various degrees. Overall mineralization capacity of Cpne7-DP was tested ex vivo PuraMatrix TM (RAD Ac-(RADA)4-NH2)…”

Section: Sld (Tdlqergdndispfsgdgqpfkd)mentioning

confidence: 99%

Bioactive Synthetic Peptides for Oral Tissues Regeneration

et al. 2021

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Regenerative therapy in oral tissues has gained relevance since tissue loss due to congenital or acquired diseases as well as trauma is a major health problem worldwide. Regeneration depends on the natural capacity of the body and the use of biomaterials and bioactive molecules that can module the processes to replace lost or damaged tissues and restore function. The combined use of scaffolds, cells, and bioactive molecules such as peptides is considered the best approach to achieve tissue regeneration. These peptides can induce diverse cellular processes as they can influence cell behavior and also can modify scaffold properties, giving as a result the enhancement of cell adhesion, proliferation, migration, differentiation, and biomineralization that are required given the complex nature of oral tissues. Specifically, synthetic peptides (SP) have a positive influence on scaffold biocompatibility since in many cases they can mimic the function of a natural peptide or a full-length protein. Besides, they are bioactive molecules easy to produce, process, and modify, and they can be prepared under well-defined and controlled conditions. This review aims to compile the most relevant information regarding advances in SP for dental and periodontal tissue regeneration, their biological effects, and their clinical implications. Even though most of the SP are still under investigation, some of them have been studied in vitro and in vivo with promising results that may lead to preclinical studies. Besides there are SP that have shown their efficacy in clinical trials such as P11-4 for enamel regeneration or caries prevention and ABM/P-15 for cementum, periodontal ligament (PDL), and alveolar bone on a previously calculus- and biofilm-contaminated zone. Also, some SP are commercially available such as PTH1-34 and PepGen P-15 which are used for bone defects treatment.

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“…In a dentin hypersensitivity model, CPNE7 induced biological dentin sealing, and the effect was permanent rather than transient [22]. Subsequently, Lee et al synthesized CPNE7-derived oligopeptide (CPNE7-DP), which, as recombinant CPNE7 protein, also induced dentinal tubule occlusion [23].…”

Section: Introductionmentioning

confidence: 99%

Desensitizing Toothpastes for Dentin Sealing and Tertiary Dentin Formation in Vitro and in Vivo: A Comparative Analysis

Lee

Hwang

Gug³

et al. 2022

Preprint

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Background Dentin hypersensitivity is a painful response to external stimuli applied to exposed dentinal tubules. Various toothpastes with active desensitizing ingredients for the relief of dentin hypersensitivity are commercially available. However, data from several studies suggest that the effects of desensitizing toothpastes are unstable and brief. This study aimed to investigate the desensitizing effect of toothpastes containing CPNE7-derived oligopeptide (CPNE7-DP) and other active desensitizing ingredients. Methods Using scanning electron microscopy (SEM), we evaluated the patency of dentinal tubules on the surface of human dentin disks after brushing experiments with the various toothpastes. Dentin was histologically evaluated in a hypersensitivity model of canine teeth, after the exposed dentin area was brushed for 6 weeks. The toothpaste used in group 1 (control) did not contain any desensitizing ingredients; that used in group 2 contained CPNE7-DP; Colgate Sensitive was used in group 3; and Sensodyne Rapid Relief was used in group 4. Finally, we conducted microleakage analysis to investigate the dentin sealing effect. Results In the SEM images, all four groups of teeth exhibited partial occlusion of the dentinal tubules on the tooth surface. In the in vivo hypersensitivity model, group 2 exhibited a newly formed tertiary dentin, whereas no new hard tissue formation was observed in groups 1, 3, and 4. Microleakage analysis revealed that the volume of dentinal fluid flow was definitely smaller in group 2 than in the other groups. Conclusions Although teeth brushed with CPNE7-DP-containing toothpaste showed partial occlusion of dentinal tubules in vitro, it induced new tertiary dentin formation with a tubular structure in the dogs’ teeth, resulting in low microleakage. These results indicate that CPNE7-DP is a promising active ingredient for the treatment of dentin hypersensitivity.

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Tubular Dentin Regeneration Using a CPNE7-Derived Functional Peptide

Cited by 25 publications

References 40 publications

CPNE7-Induced Autophagy Restores the Physiological Function of Mature Odontoblasts

CPNE7-Induced Autophagy Restores the Physiological Function of Mature Odontoblasts

Bioactive Synthetic Peptides for Oral Tissues Regeneration

Desensitizing Toothpastes for Dentin Sealing and Tertiary Dentin Formation in Vitro and in Vivo: A Comparative Analysis

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