Cpne7 deficiency induces cellular senescence and premature aging of dental pulp
Yoon Seon Lee, Yeoung‐Hyun Park, Geumbit Hwang, Hye-Jin Seo, Si Hyoung Ki, Shengfeng Bai, Chul Son, Seong Min Roh, Sujin Park, Dong‐Seol Lee, Ji‐Hyun Lee, You‐Mi Seo, Won Jun Shon, Daehyun Jeon, Mi Jang, Sahng G. Kim, Byoung‐Moo Seo, Gene Lee, Joo‐Cheol Park
Abstract
Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.