Laboratory for the Study of Regenerative Dental Medicine, Department of Oral Histology and Developmental Biology, Dental Research Institute and School of Dentistry, Seoul National University, 1 Gwanakro, Gwanak-gu, Seoul, South Korea; Regenerative Dental Medicine R & D Center, HysensBio Co., Ltd., 10 Dwitgol-ro, Gwacheon-si, Gyeonggi-do, South Korea.
Regenerative Dental Medicine R & D Center, HysensBio Co., Ltd., 10 Dwitgol-ro, Gwacheon-si, Gyeonggi-do, South Korea.
Arch Oral Biol. 2022 Nov;143:105531. doi: 10.1016/j.archoralbio.2022.105531. Epub 2022 Aug 31.
CPNE7-derived functional peptide (CPNE7-DP) has been introduced as a bioactive therapeutics for dentin diseases. CPNE7-DP regenerates tubular dentin on the pulpal side and occlude dentinal tubules. CPNE7-DP was capable to treat dentin hypersensitivity typically associated with dentinal wear at the neck of the tooth. However, the role of CPNE7-DP in another common dentin disease, dental caries, remains uninvestigated. In this study, we evaluated the potential application of CPNE7-DP in dentin caries using an experimental dentin caries model in rats.
The stability of CPNE7-DP in caries-like environments including pathologic bacteria of caries or low pH was tested. We established a nutrition-time/hyposalivation-based dental caries rat model by inoculating caries-inducing bacteria and diet for sufficient time. Glycopyrrolate has been treated to induce reversible hyposalivation for accelerating caries progression. Then the tubular dentin regeneration was investigated with histologic methods. Also, modulation of inflammation or autophagy by CPNE7-DP was investigated with marker gene expression in human dental pulp cells (hDPCs) and immunohistochemistry.
CPNE7-DP was stable with caries-inducing bacteria and low pH. Establishment of dentin caries was confirmed with radiographic and histologic evaluation. CPNE7-DP regenerated a substantial amount of tubular tertiary dentin and alleviated the pulp inflammation of dentin caries. Under inflammatory conditions, CPNE7-DP reduced the expression of inflammatory cytokines. These phenomena could be the consequence of the modulation of autophagy by CPNE7-DP, which reactivates inflamed odontoblasts.
Overall, CPNE7-DP, which repairs caries through physiological dentin regeneration, might help overcoming the limitations of current restorative caries treatments.
CPNE7 衍生的功能性肽（CPNE7-DP）已被引入作为牙本质疾病的生物活性治疗剂。CPNE7-DP 在牙髓侧再生管状牙本质并封闭牙本质小管。CPNE7-DP 能够治疗典型与牙颈部牙本质磨损相关的牙本质过敏症。然而，CPNE7-DP 在另一种常见牙本质疾病——龋齿中的作用仍未被研究。在这项研究中，我们使用大鼠实验性牙本质龋模型评估了 CPNE7-DP 在牙本质龋中的潜在应用。
测试 CPNE7-DP 在包括龋病相关细菌或低 pH 值的龋病样环境中的稳定性。我们通过接种致龋细菌和饮食足够的时间建立了基于营养时间/低唾液分泌的牙本质龋大鼠模型，以加速龋病进展。然后用组织学方法研究管状牙本质再生。此外，还通过人牙髓细胞（hDPCs）的标记基因表达和免疫组织化学研究 CPNE7-DP 对炎症或自噬的调节作用。
CPNE7-DP 与致龋细菌和低 pH 值稳定。通过放射学和组织学评估证实了牙本质龋的建立。CPNE7-DP 再生了大量的管状第三期牙本质，并减轻了牙本质龋的牙髓炎症。在炎症条件下，CPNE7-DP 降低了炎症细胞因子的表达。这些现象可能是 CPNE7-DP 通过调节自噬来实现的，自噬重新激活了发炎的成牙本质细胞。
总体而言，CPNE7-DP 通过生理性牙本质再生修复龋病，可能有助于克服当前龋病治疗的局限性。
