Dental stem cells used for gum and bone repair in periodontitis sharply lose the protein IGFBP5 with age; restoring it reverses cellular senescence markers through WNT5B suppression and markedly improves healing in rats
Dental stem cells used for gum and bone repair in periodontitis sharply lose the protein IGFBP5 with age; restoring it reverses cellular senescence markers through WNT5B suppression and markedly improves healing in rats
On September 15, biologists at Sichuan University published a paper in the International Journal of Oral Science on dental follicle stem cells, one of the types of dental stem cells considered promising for treating periodontitis. The authors identified a protein whose disappearance triggers senescence in these cells and showed that restoring it reverses the process, both in human cell culture and upon transplantation into rats with periodontitis.
Dental follicle stem cells (immature cells from beneath a still-unerupted tooth) are among the most convenient cell sources for periodontal regeneration: the restoration of the tissues that anchor a tooth in bone. A related type, dental pulp stem cells, has already been tested in humans: a 2025 trial showed that donor injections improve outcomes in periodontitis, which in its severe form affects more than a billion people. These cells undergo senescence (whether in prolonged culture or when taken from an older donor) and then engraft less well and heal less effectively: an August review of cell therapy called this a general weakness of cell-based products.
Biologists at Sichuan University compared the RNA of young cells with that of cells aged by oxidative stress or by serial passaging and, without a prior hypothesis, identified IGFBP5. This protein was already known as one of the factors that help stem cells differentiate into bone, but its link to cellular senescence had not been examined. In both aging models it ranked among the most sharply downregulated genes, dropping 69-fold during serial passaging. Causality was tested in both directions: silencing the IGFBP5 gene in young cells triggered senescence on its own, sharply reducing their ability to form bone, while restoring IGFBP5 in senescent cells reversed the senescence markers and recovered that ability.
The mechanism is specific: IGFBP5 suppresses a single branch of the Wnt pathway, a signaling family that governs cell division, senescence, and differentiation. It lowers the level of WNT5B and of the downstream effector c-Jun, both of which push the cell toward senescence; the canonical branch of Wnt signaling is unaffected. Adding WNT5B to cells with restored IGFBP5 partially reversed the protection, confirming the direction of causality. In the replicative-senescence model, where restoring IGFBP5 directly was not feasible because aged cells engrafted poorly, the same axis was targeted through an antibody against WNT5B, and senescence was partially reduced.
The authors carried the finding through to a therapeutic test. The team assembled a hydrogel loaded with hydroxyapatite nanoparticles (the mineral that makes up bone) and seeded it with IGFBP5-restored cells. In rats with periodontitis this hydrogel carrying the rejuvenated cells regenerated bone more effectively than either an empty hydrogel or the same hydrogel with unmodified cells: bone density and volume were higher, inflammation was lower, collagen was denser, and osteogenic protein expression was stronger. In the treated tissue, GLB1 (a marker of cellular senescence) decreased while IGFBP5 rose and WNT5B fell: the same pair of shifts that had reversed senescence in cell culture.
According to the authors, the clinical significance of this work is that rejuvenating senescent cells before implantation substantially enhances periodontal bone regeneration compared with transplanting unmodified stem cells. They describe this strategy as promising for other age-related bone disorders as well.