IADR Abstract Archives
Wnt Signaling Regulates Location-specific Osteogenic Potential in Craniofacial Bone
Objectives: Clinicians have long observed that defects of similar size heal disparately on different parts of the craniofacial bone, and such a discrepancy has been attributed to the micro-structure at the injury sites. Type-III cancellous bone is generally considered more efficient in healing than type I cortical bone, but no concrete experimental proof exists. In this study, we set out to approach the cellular and molecular basis underlying the location-specific osteogenic potential in craniofacial bone.
Methods: Two representative locations on murine maxillae were chosen for comparison. The edentulous bone between incisors and molars represented the cortical bone, and the alveolae supporting molars represented the cancellous bone. Their ultra-structure was examined using histological staining, micro-CT scanning, and scanning electron microscopy. Osteogenic activities at both intact and injured state were evaluated with histochemistry, immunohistochemistry, and qRT-PCR. Furthermore, Axin2lacZ and Axin2Cre/Ert2;R26mTmG transgenic models were employed to map the expression pattern of Wnt signaling and identify the role of Wnt-responsive cell during craniofacial bone repair.
Results: Edentulous and alveolar bone differed sharply in density, matrix organization, and osteocyte morphology. Alveolar bone presented significantly higher level of osteogenic marker expression and accordingly healed more readily after drill injury or implant insertion. Evaluation of Axin2LacZ/+ samples revealed significantly more Wnt-responsive cells at alveolar bone and this population was highly osteogenic. Lineage tracing performed on Axin2Cre/Ert2;R26mTmG mice showed that Wnt-responsive cells migrated into the injury site and contributed directly to new bone formation. Furthermore, enhancing Wnt signaling through either exogenous Wnt3a protein injection or endogenous Axin2 knockout efficiently improved injury healing at edentulous bone.
Conclusions: Craniofacial bone homeostasis is highly correlated with Wnt signaling in a location-specific manner. Since Wnt-responsive cells are directly responsible for the bone healing, Wnt signaling may be a potential modulating target for improving the prognosis of craniofacial bony defect.
Methods: Two representative locations on murine maxillae were chosen for comparison. The edentulous bone between incisors and molars represented the cortical bone, and the alveolae supporting molars represented the cancellous bone. Their ultra-structure was examined using histological staining, micro-CT scanning, and scanning electron microscopy. Osteogenic activities at both intact and injured state were evaluated with histochemistry, immunohistochemistry, and qRT-PCR. Furthermore, Axin2lacZ and Axin2Cre/Ert2;R26mTmG transgenic models were employed to map the expression pattern of Wnt signaling and identify the role of Wnt-responsive cell during craniofacial bone repair.
Results: Edentulous and alveolar bone differed sharply in density, matrix organization, and osteocyte morphology. Alveolar bone presented significantly higher level of osteogenic marker expression and accordingly healed more readily after drill injury or implant insertion. Evaluation of Axin2LacZ/+ samples revealed significantly more Wnt-responsive cells at alveolar bone and this population was highly osteogenic. Lineage tracing performed on Axin2Cre/Ert2;R26mTmG mice showed that Wnt-responsive cells migrated into the injury site and contributed directly to new bone formation. Furthermore, enhancing Wnt signaling through either exogenous Wnt3a protein injection or endogenous Axin2 knockout efficiently improved injury healing at edentulous bone.
Conclusions: Craniofacial bone homeostasis is highly correlated with Wnt signaling in a location-specific manner. Since Wnt-responsive cells are directly responsible for the bone healing, Wnt signaling may be a potential modulating target for improving the prognosis of craniofacial bony defect.