The Role of Sfrp4 in Alveolar Bone and Incisor Tooth Extraction Socket Healing

Abstract

Objectives: The purpose of this study is to explore the effects of Sfrp4 deletion on alveolar bone and healing of incisor tooth extraction sockets.

Introduction: There are many genetic and development bone diseases that affect the skeletal system and compromise the quality and strength of bone. Among these is Pyle’s disease OMIM-265900). Pyle’s disease is a disorder of bone architecture characterized by expanded trabecular metaphyses, thin cortical bone, and bone fragility. Our laboratory has linked Pyle’s disease to loss of function mutations of Secreted Frizzled Receptor Protein 4 (sFRP4). sFRP4 is a member of the Wnt signaling that functions as a Wnt decoy receptor and blocks all Wnt signaling cascades.

Pyle disease’s patients present with abnormal cortical bone in the craniofacial skeleton, smaller heads, thin calvarium and expanded diploe, as well as dental abnormalities such as tooth decay, delayed tooth eruption, and retained deciduous teeth. However, the role of sFRP4 deficiency in alveolar bone and tooth extraction healing is not known.

Methods: Maxillary right incisor extractions were performed on 8 weeks (wk) old WT and Sfrp4-/- (KO) male and female mice. Mice were sacrificed one, two, and three wk after tooth extraction. Skulls were harvested for three-dimensional micro-computed tomographic (uCT) and bone histomorphometry.

Bone morphometry and 3D reconstruction were performed for both groups to explore Sfrp4 deficiency effects on alveolar bone in maxillary incisor and molars areas. The healing socket of the extracted maxillary right incisor was analyzed by uCT, dynamic, and cellular bone histomorphometry.

Results: Sfrp4 deletion resulted in significantly decreased bone volume and increased porosity in alveolar bone of incisor and molars areas. However, Sfrp4 deletion did not show a significant difference in bone healing of incisor tooth socket.

Conclusion: Similar to the phenotype seen in long bones, in alveolar bone, Sfrp4 deletion leads to a significant decrease in cortical bone volume and increased porosity in both the incisor and molars alveolar bone areas.

Incisor socket bone healing is not affected by Sfrp4 deletion, suggesting that simultaneous activation of canonical and non-canonical Wnt cascades by Sfrp4 deletion does not impair socket bone healing. These findings might have direct clinical applications as patients with Pyle’s disease usually presents with dental abnormalities requiring tooth extraction.