Tristetraprolin (TTP) is an RNA-binding protein that targets numerous immunomodulatory mRNA transcripts for degradation. Many TTP targets are key players in the pathogenesis of periodontal bone loss, including tumor necrosis factor-α. To better understand the extent that host immune factors play during periodontal bone loss, we assessed alveolar bone levels, inflammation and osteoclast activity in periodontal tissues, and immune response in draining cervical lymph nodes in TTP-deficient and wild-type (WT) mice in an aging study. WT and TTP-deficient (knockout [KO]) mice were used for all studies under specific pathogen-free conditions. Data were collected on mice aged 3, 6, and 9 mo. Microcomputed tomography (µCT) was performed on maxillae where 3-dimensional images were generated and bone loss was assessed. Decalcified sections of specimens were scored for inflammation and stained with tartrate-resistant acid phosphate (TRAP) to visualize osteoclasts. Immunophenotyping was performed on single-cell suspensions isolated from primary and peripheral lymphoid tissues using flow cytometry. Results presented indicate that TTP KO mice had significantly more alveolar bone loss over time compared with WT controls. Bone loss was associated with significant increases in inflammatory cell infiltration and an increased percentage of alveolar bone surfaces apposed with TRAP+ cells. Furthermore, it was found that the draining cervical lymph nodes were significantly enlarged in TTP-deficient animals and contained a distinct pathological immune profile compared with WT controls. Finally, the oral microbiome in the TTP KO mice was significantly different with age from WT cohoused mice. The severe bone loss, inflammation, and increased osteoclast activity observed in these mice support the concept that TTP plays a critical role in the maintenance of alveolar bone homeostasis in the presence of oral commensal flora. This study suggests that TTP is required to inhibit excessive inflammatory host responses that contribute to periodontal bone loss, even in the absence of specific periodontal pathogens.
Based upon available experimental data, a set of empirical equations was derived for nasal deposition efficiency of inhaled particles in the inertial deposition range for four small laboratory animal species: the mouse, hamster, rat, and guinea pig. An equation for nasal deposition in humans was also derived in the same mathematical form to facilitate interspecies comparison. In these equations, deposition efficiency was expressed as a function of particle inertia d :~ where d , is the particle aerodynamic diameter and Q is the flow rate. Results from the empirical equations showed that nasal deposition was species dependent, and that a t the same d :~, species with smaller body weight had higher deposition efficiency. By incorporating the anatomical data of the nasal passage, the deposition equations were rewritten as a function of the product of Stokes number and the total bend angle in nasopharynx. Interspecies deposition differences were found to be greatly reduced in terms of the new variable.
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