Tristetraprolin is Essential to Maintain Alveolar Bone Homeostasis

Tristetraprolin (TTP) is a key RNA-binding protein that regulates pro-inflammatory cytokines post-transcriptionally by binding to adenylate-uridylate-rich elements (AREs) within the 3’-unstranslated (UTR) region. During inflammation, the p38 mitogen activated protein kinase (MAPK) pathway inactivates TTP by phosphorylation to inhibit its ability to shuttle mRNA to cytoplasmic degradation machinery. Interestingly, TTP knockout mice exhibit an inflammatory phenotype of arthritis, myeloid hyperplasia, and cachexia. We hypothesize that TTP directs cytokine expression in inflammatory bone loss during periodontal disease progression. Objective: The purpose of this study is to determine if depletion of TTP affects alveolar bone loss and inflammation associated with periodontal disease progression under specific pathogen free (SPF) housing conditions. Methods: We compare TTP ^-/- (n=6) and TTP^+/- (n=5) to wild type control mice (n=4). Sites of maxillary interradicular bone and furcation areas were used for comparison by micro computed tomography (μCT) using bone volume fraction.  Histological examination was used to quantify the degree of inflammatory infiltrate. Results: Remarkably, without any inflammatory stimulation other than exposure to oral commensal bacteria, both TTP^-/- and TTP^+/- have significantly more inflammatory infiltrate and basal bone volume is quantitatively less in TTP^+/- and TTP^-/- mice compared to wild type controls. Conclusion: These preliminary data suggest that TTP may potentially function to maintain alveolar bone homeostasis in mice housed under SPF housing conditions.