Original Full Length ArticleAnti-DKK1 antibody promotes bone fracture healing through activation of β-catenin signaling

- The role of DKK1-Ab in fracture healing has been determined.
- Treatment with DKK1-Ab accelerated fracture healing in mice.
- Deletion of β-catenin in mesenchymal progenitor cells leads to bone mass reduction.
- DKK1-Ab lost its stimulatory effect on fracture healing in β-catenin KO mice.
- Our findings suggest that DKK1-Ab promoted fracture healing through activation of β-catenin signaling.

In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-cateninPrx1ER conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing process in CD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-cateninPrx1ER conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention.