Stem Cell Breakthrough: Two Dental Stem Cell Types Could Regrow Teeth and Jawbone

Stem cell study identifies cell types that may regenerate teeth and alveolar bone

Tooth loss and bone deterioration remain major clinical challenges. According to the National Bone Health Policy Institute, about 10 million Americans aged 50+ have been diagnosed with osteoporosis, and many more show low bone density. The Centers for Disease Control and Prevention report that at least 11% of older adults have lost all their teeth. Regenerating teeth and the supporting jawbone (the alveolar bone) would be a major medical advance with broad implications for oral health and quality of life.

What the new study found

Published in Nature Communications (2025) and titled "A Hedgehog–Foxf axis coordinates dental follicle-derived alveolar bone formation," the study identifies two stem cell populations in the dental follicle that give rise to the osteoblasts and osteocytes responsible for forming and maintaining alveolar bone. Using genetically engineered mice to trace PTHrP-expressing dental follicle cells, the researchers showed that these marked cells predominantly mature into bone-forming cells near developing teeth.

How signaling controls bone formation

The team examined the Hedgehog signaling pathway, a well-known regulator of growth and differentiation. They found that Hedgehog-related genes are highly active during the early stages of tooth root and alveolar bone formation, then fall to almost undetectable levels once maturation is complete. This temporal on‑and‑off pattern is essential: turning Hedgehog signaling off at the right time permits stem cells to progress into mature osteoblasts and osteocytes.

Disease relevance and drug testing

When comparing healthy tissue to bone affected by periodontitis, the researchers observed elevated Hedgehog activity in diseased bone during episodes of bone loss. That suggests pathologic reactivation of Hedgehog signaling may impede normal bone maturation. Encouragingly, treatment with an FDA-approved Hedgehog inhibitor, LDE225, restored normal bone cell development and stability in the researchers' models without detectable harm to healthy tissue, indicating potential for therapeutic repurposing or refinement.

Role of Foxf1

The study also implicates transcription factors in the Fox family, particularly Foxf1. Foxf1 became overactive when Hedgehog signaling was turned on, and reducing Foxf1 activity helped rescue normal bone growth patterns. This positions Foxf1 as a likely intermediary that controls whether dental follicle stem cells become bone-forming cells—and therefore as a promising target for regenerative strategies.

Broader implications and next steps

These findings outline a Hedgehog–Foxf regulatory axis that shapes how dental follicle stem cells produce alveolar bone. The authors note further research is needed to map the full regenerative potential of dental cells and to translate these discoveries into clinical therapies. Parallel work on genes such as GPR133 (ADGRD1), which has been proposed as a target to address systemic bone loss like osteoporosis, may complement strategies aimed at restoring teeth and jawbone.

Bottom line: Precise timing of Hedgehog signaling and modulation of Foxf1 appear critical for dental follicle stem cells to form healthy alveolar bone. Targeting this pathway could open new avenues to regenerate teeth and rebuild jawbone lost to disease or injury.

Source: Adapted from a 2025 study in Nature Communications titled "A Hedgehog–Foxf axis coordinates dental follicle-derived alveolar bone formation."