| First Author | Jin H | Year | 2015 |
| Journal | Bone | Volume | 71 |
| Pages | 63-75 | PubMed ID | 25263522 |
| Mgi Jnum | J:232450 | Mgi Id | MGI:5779261 |
| Doi | 10.1016/j.bone.2014.07.039 | Citation | Jin H, et al. (2015) Anti-DKK1 antibody promotes bone fracture healing through activation of beta-catenin signaling. Bone 71:63-75 |
| abstractText | In this study we investigated if Wnt/beta-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of beta-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in beta-catenin(Prx1ER) conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (muCT), 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 beta-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through beta-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in beta-catenin(Prx1ER) 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. |
