Wnt Signaling Regulates Location-specific Osteogenic Potential in Craniofacial Bone

Objectives: Clinicians have long observed that implants osseointegrate with varying efficiency on different parts of the craniofacial bone, and such discrepancy has been attributed to the micro-structure at the recipient sites. TypeIII cancellous bone is generally considered more efficient at healing than type I cortical bone, but no concrete experimental proof exists. In this study, we set out to determine 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 compact lamellar bone of the edentulous ridge between incisors and molars, analogous to cortical bone, was compared with the adjacent alveolar bone-supporting molars, analogous to 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, Axin2^lacZ and Axin2^Cre/Ert2;R26^mTmG transgenic models were employed to map Wnt signaling activity and examine the role of Wnt-responsive cells during craniofacial bone repair.

Results: Edentulous and alveolar bone differed sharply in density, matrix organization, and osteocyte morphology. Alveolar bone displayed a significantly higher level of osteogenic marker expression and healed more readily after drill injury or implant insertion[GV3] . Evaluation of Axin2^LacZ/+ samples revealed significantly more Wnt-responsive cells within alveolar bone and that this population was highly osteogenic. Lineage tracing performed on Axin2^Cre/Ert2;R26^mTmG 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 improved both injury healing and implant osseointegration at edentulous bone.



Conclusions: Craniofacial bone homeostasis is highly correlated with Wnt signaling in a location-specific manner. Since Wnt-responsive cells contribute to bone healing, Wnt signaling may be a potential target for modulation to improve the prognosis of implants.