West China School of Stomatology New Study: IGFBP5 Can Alleviate Dental Follicle Stem Cell Senescence and Promote Periodontal Bone Regeneration

Source: IGFBP5 alleviates periodontitis by reversing human dental follicle stem cell senescence via the non-canonical Wnt pathway

DentalGoodNews｜On September 15, 2026, a research team from Sichuan University West China Hospital of Stomatology published their latest study in the International Journal of Oral Science (Nature Portfolio), identifying IGFBP5 as an important regulatory factor in the senescence of human Dental Follicle Stem Cells (DFSCs). Through in vitro and rat experiments, the team demonstrated that overexpression of IGFBP5 can alleviate DFSC senescence and restore part of their osteogenic differentiation potential; combined with a novel composite hydrogel scaffold, it can promote periodontal bone regeneration in a rat periodontitis model.

The research team stated that Dental Follicle Stem Cells, as cells with strong proliferative and multilineage differentiation potential, play a role in maintaining periodontal tissue homeostasis and damage repair. However, with cellular senescence, their tissue maintenance and repair capacity may be affected; in the periodontitis environment, stem cell senescence may also exacerbate local inflammation and affect bone remodeling.

In this study, RNA sequencing analysis revealed that IGFBP5 showed a downregulated trend in both oxidative stress-induced and replicative senescent DFSC models (downregulated up to 69-fold in the RS model). Experimental results showed that after overexpression of IGFBP5 via a lentiviral system, the SA-β-gal positive rate of senescent cells was significantly reduced, senescence markers such as P16 and P21 were downregulated, and intracellular reactive oxygen species (ROS) levels were decreased, with cell viability and osteogenic mineralization capacity partially restored.

Source: IGFBP5 alleviates periodontitis by reversing human dental follicle stem cell senescence via the non-canonical Wnt pathway

At the molecular mechanism level, the study found that IGFBP5 mainly affects the non-canonical Wnt signaling pathway. After IGFBP5 overexpression, the levels of non-canonical Wnt pathway-related proteins WNT5B, c-Jun, and phosphorylated c-Jun were all decreased, while no significant changes were observed in the canonical Wnt/β-catenin pathway. The study further found that exogenous rhWNT5B protein could partially attenuate the pro-osteogenic effects brought by IGFBP5 overexpression, supporting WNT5B as a downstream regulatory factor of IGFBP5 participating in this process.

To explore the translational application of the research findings, the research team also developed a vinyl-functionalized Nano Hydroxyapatite (n-HAp) (vHA)-reinforced GelMA composite hydrogel scaffold (Gel-vHA). By integrating vHA into the GelMA network, this material improved the compressive modulus and stability of the scaffold, and was used to carry IGFBP5-overexpressing DFSCs for animal experimental validation.

Source: IGFBP5 alleviates periodontitis by reversing human dental follicle stem cell senescence via the non-canonical Wnt pathway

In a rat molar periodontitis model, after 4 weeks of treatment, imaging showed that the bone mineral density (BMD) and bone volume fraction (BV/TV) of the Gel-vHA@oe-DFSC group were increased compared with the corresponding control group, and the CEJ-ABC distance was significantly shortened; histological observation showed that this group exhibited denser collagen fiber reconstruction.

This study suggests that IGFBP5 has application value as a molecular indicator of DFSC senescence and a potential therapeutic target. However, the current research is still at the cellular and animal experimental stage, and human clinical validation has not yet been conducted; the safety and efficacy of the related conclusions in human clinical applications still require further research and validation.