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Metabolic programming in tooth development: a regulatory network from energy substrates to signaling instructions
Xiaoyu Cao1, Yiping Gao1,2, Wen Liu1,2
1Department of Oral Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Frontiers in Cell and Developmental Biology
|March 23, 2026
Summary
Metabolism actively programs tooth development by interacting with signaling pathways, going beyond basic energy supply. This metabolic-signaling crosstalk guides tooth formation and mineralization, offering new therapeutic targets.
Area of Science:
- Developmental Biology
- Metabolic Regulation
- Oral Medicine
Background:
- Tooth development relies on complex signaling networks.
- Metabolism was traditionally seen as only providing energy and building blocks.
Purpose of the Study:
- To propose metabolism as an active programmer in tooth development.
- To elaborate a dynamic metabolic regulatory framework integrating metabolism and signaling pathways.
Main Methods:
- Systematic integration of recent evidence on metabolism and tooth development.
- Analysis of four core mechanisms of metabolic-signaling crosstalk.
- Review of evidence from metabolic disorder models.
Main Results:
- Metabolism actively programs tooth development through bidirectional crosstalk with signaling pathways (Wnt, BMP, FGF, Hh).
- Four core mechanisms mediate this crosstalk: energy sensing, enzyme signaling, epigenetic remodeling, and substrate metabolism.
- This network guides cell behavior, tooth morphogenesis, and matrix mineralization.
Conclusions:
- Metabolic status plays a central regulatory role in tooth development.
- Understanding this metabolism-signaling network is crucial for elucidating developmental principles and disease mechanisms.
- Targeting metabolic nodes holds translational potential for diagnosis, prevention, and regenerative therapy in oral medicine.
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