A Wnt-Responsive PDL Population Effectuates Extraction Socket Healing

Abstract

Stem cells residing in the periodontal ligament (PDL) support the homeostasis of the periodontium, but their in vivo identity, source(s), and function(s) remain poorly understood. Here, using a lineage-tracing mouse strain, we identified a quiescent Wnt-responsive population in the PDL that became activated in response to tooth extraction. The Wnt-responsive population expanded by proliferation, then migrated from the PDL remnants that remained attached to bundle bone, into the socket. Once there, the Wnt-responsive progeny upregulated osteogenic protein expression, differentiated into osteoblasts, and generated the new bone that healed the socket. Using a liposomal WNT3A protein therapeutic, we showed that a single application at the time of extraction was sufficient to accelerate extraction socket healing 2-fold. Collectively, these data identify a new stem cell population in the intact periodontium that is directly responsible for alveolar bone healing after tooth removal.