Role of Dendritic Cells in Post-Extraction Alveolar Bone Healing

Abstract

Dendritic cells (DCs) are considered the main antigen presenting cells in the body. They are an essential link between innate and adaptive immunity. The plasticity of DCs allows them to initiate an immune response against foreign antigens while maintaining tolerance to commensal microbes. DCs have been recognized as important players in osteoimmunology through their role in regulation of inflammation-induced bone loss. DCs have been identified in inflammatory synovial and periodontal tissues, where they interact with activated T cells to form aggregates called lymphoid foci. DCs have shown an indirect role in inflammation-induced bone loss through activation of RANKL-producing T cells. However, a direct role has also been implicated through the ability of some DC subsets to transdifferentiate into osteoclasts. Although the role of DCs in inflammation-induced bone loss is well recognized, their role in alveolar bone healing and repair remains to be elucidated. We hypothesize here that ablation of DCs in the oral microenvironment will have a negative effect on alveolar bone healing following a maxillary molar extraction in mice due to disruption of osteo-immune homeostasis. Our hypothesis was tested using a classical dendritic cell ablation mouse model, in transgenic Zbtb46 tm1 (DTR)Mnz/J (ZDC-DTR) mice, which are rendered DC deficient by diphtheria toxin injection. Histological analysis of photomicrographs of bone sections at the extraction sites showed a significant increase in osteocyte death in the DC-deficient animals compared to wild type (WT) animals which had normal DC number and activity. Further, the animals deficient in DCs showed less bone regeneration in the extraction socket compared with WT animals. Our results shed light on the important role of DCs in post-extraction homeostasis of alveolar bone healing, allowing for a better understanding of the complex biological process of bone healing.