What the study tested
Ke and colleagues asked whether the forkhead-box transcription factor Foxq1, which they found highly expressed in odontoblasts relative to donor-matched osteoblasts in a published gene-expression data set (GSE119897), controls the polarization step that turns a mineral deposit into organized tubular dentine. They focused on dental papilla stem cells (DPSCs) isolated from embryonic day 14.5 (E14.5) mouse molar mesenchyme and on acellular human dentine as a scaffold. The work is reported in the International Endodontic Journal as a laboratory investigation.
Key in-vitro findings
Foxq1 expression tracked with active dentine formation: it was detectable at E11.5, enriched in dental mesenchyme by E14.5, and peaked between postnatal days 3 and 7, when dentine maturation is most active. In E14.5 tooth-germ organ culture, Foxq1 overexpression increased dentine area and thickened the dentine layer, while short-hairpin-RNA knockdown reduced tooth-germ size, disrupted odontoblast polarity, and lowered dentine formation.
In cultured DPSCs, Foxq1 overexpression upregulated odontogenic markers (Dlx1, Dlx2, Msx1, Msx2, Dmp1, Pax9) and polarity genes (Pard3, Ezr, Tjp1), whereas knockdown had the opposite effect. Recombinant WNT5A protein rescued the polarity and dentine defects caused by Foxq1 suppression.
Mechanism: promoter binding and direct interaction
The authors provide two lines of evidence that Foxq1 and Wnt5a are coupled. Co-immunoprecipitation and surface plasmon resonance showed a physical interaction between FOXQ1 and WNT5A protein, with an equilibrium dissociation constant of 3.94 nM. Dual-luciferase reporter and chromatin immunoprecipitation assays further showed that Foxq1 binds directly to promoter regions of both Wnt5a and the dentine marker Dspp.
In-vivo outcome and its boundary
For the animal experiment, the group seeded E14.5 DPSCs (1 million cells) in a fibrin gel inside acellular human incisor or premolar root scaffolds and implanted them subcutaneously in 5-week-old male Kunming mice for eight weeks. Micro-CT and histology showed that Foxq1-overexpressing and Wnt5a-overexpressing DPSCs both produced de novo tubular-dentine-like tissue along the inner dentine wall, whereas vector-control cells produced little hard tissue.
The result comes with an important limit: where the scaffold had no opening into existing tubular dentine, the cells formed irregular osteodentin rather than organized tubular dentine. The scaffold geometry, not the cell modification alone, determined whether the tissue was dentine-like or bone-like.
Why it matters for the pulp-dentin repair route
Most dentine-repair strategies activate BMP or canonical Wnt signaling and often produce osteodentin. Ke et al. identify a Foxq1-Wnt5a axis as a candidate regulator of the polarization step that produces tubular architecture. Because the work was done in mouse cells and a subcutaneous mouse model, it does not establish clinical feasibility, but it does give a mechanistic rationale for engineering polarized dentine formation inside an existing root canal. The finding is consistent with the route’s broader goal: regenerate pulp-dentin complex function rather than simply fill the space.
Source verified against the primary paper: Ke J, Zhang M, Kong L, Chung H, Wu X, Ai T, Zheng J, Li Y, Cao Y, Ling J, Xiang L. Foxq1-Wnt5a axis activation in dental papilla stem cells promotes odontogenesis on acellular matrix: a laboratory investigation. Int Endod J. 2026;59(8):1694-1709. doi:10.1111/iej.70160. For editorial standards and tier definitions, see /method/.