What the research is about
Teeth function not only because of the hard enamel on the surface, but also because they have roots that anchor them firmly in the jawbone beneath the gums. Eating, speaking, and maintaining the shape of the face-teeth are essential for supporting our daily lives.
It has been known that the apical papilla (AP), located at the tip of the developing tooth root, contains multiple types of AP cells, including stem cells involved in forming the root. However, which cells act in what manner, and by what mechanism the tooth root is formed, have remained unclear.
Why this matters
A research group including Assistant Professor Mizuki Nagata of Institute of Science Tokyo (Science Tokyo), Professor Wanida Ono of the University of California, San Francisco, and Professor Noriaki Ono of the University of Texas discovered that, at the same time tooth root formation begins, a distinct population of AP cells that secrete a factor called CXCL12 (CXCL12+ AP cells) emerges. The team further demonstrated that these specialized cells function as a "command center," cooperating with other AP cells to drive tooth root formation.
A closer analysis of these command center cells-CXCL12+ AP cells-revealed an additional, unexpected finding. These cells can turn into both odontoblasts, which form dentin (the hard tissue on the inside of the tooth), and cementoblasts, which form cementum (the thin outer layer covering the root). Traditionally, these two cell types were thought to arise from separate cell populations; in contrast, the present study shows that a single cell population shapes both the inner and outer structures of the tooth root.
The researchers also found that proper function of CXCL12+ AP cells depends on two signaling pathways within the AP: Wnt signaling and TGF-β signaling. Wnt signaling guides CXCL12+ AP cells to the appropriate location and acts as a switch that activates their root-forming function. TGF-β signaling was also found to act in concert with Wnt signaling during root formation. In other words, the balance between these two signals-Wnt and TGF-β-is key to ensuring correct progression of tooth root formation.
What's next
This discovery has the potential to contribute not only to revealing the mechanisms of tooth root formation, but also to regenerative therapies and stem cell-based treatments aimed at restoring tooth roots. If tooth roots could be regenerated using one's own cells, it may become possible to regain a natural biting sensation that cannot be achieved with artificial teeth. The newly identified CXCL12+ AP cells are attracting attention as "seed cells" that could be used for such regeneration.
Moreover, although these command center cells are normally specialized for forming tooth roots, they also possess the flexibility to change roles depending on circumstances. For example, when tissues surrounding the tooth are damaged or when repair of the jawbone becomes necessary, they can also become osteoblasts, the cells that form bone. Applications to regenerative medicine for tooth roots and the jawbone are therefore becoming increasingly realistic.
Comment from the researcher
The tooth root is an important tissue not only for maintaining healthy teeth, but also for keeping the surrounding bone-and ultimately the entire oral cavity-healthy. Understanding the mechanisms underlying its formation is a theme that extends beyond dental research alone and connects to regenerative medicine for the body as a whole.
By gaining a deeper understanding of the roles of stem cells in the body, I believe it will eventually lead to new treatments that can more efficiently regenerate teeth and bone lost to dental caries or periodontal disease.
(Mizuki Nagata: Assistant Professor, Department of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo)
