Dental Pulp Stem Cell Subsets Triggers Rapid Cellular Senescence and Tooth Decay

With age, teeth get increasingly brittle and susceptible to damage from tooth decay, which can eventually lead to tooth loss. Teeth have an intrinsic capability to regenerate, a process which is driven by dental pulp stem cells (DPSCs) which replenish the dental pulp including the dentin-producing cells called odontoblasts.

DPSCs stops working in aging teeth, divide less, and generate less odontoblasts, a process which is called senescence or the biological process of aging through gradual deterioration. DPSC senescence is thought to be a cause for the declining tooth health with age. 

A research team led by Fanyuan Yu from Sichuan University, China, has now discovered one of the mechanisms of DPSC senescence and identified a potential strategy to counter it. In their work published today in the journal Stem Cell Reports, the researchers first compared the regenerative capacity of young and old human molars affected by severe tooth decay. While most of the young teeth could be preserved, more than half of the aged teeth eventually died off, suggesting that tooth aging impairs dental pulp regeneration. 

To explain this phenomenon, Yu's team used genetically engineered mouse models to identify a distinct subset of DPSCs responsible for generating new dental pulp cells and odontoblasts in young teeth. These stem cells were nearly absent in the teeth of old mice. Further, when these stem cells were eliminated from the teeth of young mice, the dental pulp underwent senescence and contained significantly less odontoblasts, further underscoring the essential role of this DPSC subset in tooth regeneration. 

A unique feature of these stem cells was the expression of a protein called NFATC1, which was abundant in young DPSCs but significantly reduced in old cells in both mouse and human teeth. NFATC1 was essential for the proper function of the mouse DPSCs, as its deletion halted odontoblast generation, induced senescence in young teeth, and reduced the tooth's ability to regenerate after injury. Encouragingly, tooth regeneration could be stimulated in NFATC1 deficient mice by a combination of "senolytic" drugs which act by eliminating senescent cells. 

This study shows that a specific type of NFATC1+ DPSCs is essential for tooth regeneration and to prevent senescence. Follow-up studies will be required to show if preserving these stem cells can counteract tooth aging.