Researchers at The University of Texas at San Antonio Health Science Center are investigating how the body forms dentin, the hard tissue beneath tooth enamel, and how understanding this natural process could one day help regenerate dental tissue and repair damaged teeth.
Shuo Chen, MD, PhD, professor of developmental dentistry at the UT San Antonio School of Dentistry, studies the molecular mechanisms that regulate dentin formation and inherited dentin disorders. His research focuses particularly on dentin sialophosphoprotein (DSPP), a protein that produces specialized cells that form dentin.
Chen recently received a five-year renewal of his National Institutes of Health (NIH) R01 research grant from the National Institute of Dental and Craniofacial Research (NIDCR). The funding will allow his research team to continue investigating the molecular mechanisms of dentin formation using animal models and to explore how these mechanisms might eventually be applied to repair damaged teeth.
The long-term goal is to establish a biological foundation for dentin regeneration and, ultimately, contribute to the development of “bio-teeth” by harnessing the body’s natural processes to restore tooth structure and function.
Understanding DSPP
DSPP plays an essential role in dentin formation. Mutations in the DSPP gene are associated with inherited dentin disorders, including dentinogenesis imperfecta, which can lead to translucent or discolored teeth, and dentin dysplasia, which causes misshapen teeth or teeth without roots.
After DSPP is produced, it is processed into two major protein components: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). DSP can undergo further processing to generate biologically active regions, or domains. Chen’s research focuses primarily on DSP and the biological functions of its specific domains.
Chen’s research focuses on the molecular interactions within the DSP that regulate cellular behavior, with the aim of determining how these interactions contribute to dentin development and regeneration.
Chen said the new research builds on findings from the previous grant period, which advanced understanding of how DSP regulates blood vessel development and influences the differentiation of cells involved in dentin formation and regeneration.
Connection between blood vessels and dentin
The relationship between blood vessel development and dentin formation is an important component of Chen’s research.
The dental pulp, located within the tooth’s central chamber, contains blood vessels, nerve fibers, connective tissue and various cell populations that support tooth health. Blood vessels supply oxygen and nutrients that help maintain the living tissues inside the tooth.
Chen’s research suggests that DSP signaling may influence blood vessel development through interactions that can activate intracellular signaling that promote the development of cells involved in blood vessel formation. Understanding this mechanism could provide new insights into how the vascular environment supports dentin formation, tooth maintenance and tissue regeneration.
A step toward the “bio-tooth”
Chen’s research contributes to the broader goal of developing new strategies that harness the body’s own biological processes to repair, regenerate and restore damaged teeth.
Although the development of a fully functional biological replacement tooth remains a long-term goal, understanding the molecular mechanisms that regulate dentin formation is an important step toward that vision.
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Related research:
Xu X, Fu J, Yang G, Chen Z, Chen S, Yuan G. Dentin sialoprotein promotes endothelial differentiation of dental pulp stem cells through DSPaa34-50-endoglin-AKT1 axis. J Biol Chem. 2025 Apr;301(4):108380. doi: 10.1016/j.jbc.2025.108380. Epub 2025 Mar 4. PMID: 40049415; PMCID: PMC11997338.
Xu X, Fu J, Yang G, Chen Z, Chen S, Yuan G. Dentin sialoprotein acts as an angiogenic factor through association with the membrane receptor endoglin. J Biol Chem. 2025 Mar;301(3):108279. doi: 10.1016/j.jbc.2025.108279. Epub 2025 Feb 6. PMID: 39922489; PMCID: PMC11910139.