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.
Although there is a clear relationship between the degree of obesity and periodontal disease incidence, the mechanisms that underpin the links between these conditions are not completely understood. Understanding that myeloid-derived suppressor cells (MDSCs) are expanded during obesity and operate in a context-defined manner, we addressed the potential role of MDSCs to contribute toward obesity-associated periodontal disease. Flow cytometry revealed that in the spleen of mice fed a high-fat diet (HFD), expansion in monocytic MDSCs (M-MDSCs) significantly increased when compared with mice fed a low-fat diet (LFD). In the osteoclast differentiation assay, M-MDSCs isolated from the bone marrow of HFD-fed mice showed a larger number and area of osteoclasts with a greater number of nuclei. In the M-MDSCs of HFD-fed mice, several osteoclast-related genes were significantly elevated when compared with LFD-fed mice according to a focused transcriptomic platform. In experimental periodontitis, the number and percentage of M-MDSCs were greater, with a significantly larger increase in HFD-fed mice versus LFD-fed mice. In the spleen, the percentage of M-MDSCs was significantly higher in HFD-fed periodontitis-induced (PI) mice than in LFD-PI mice. Alveolar bone volume fraction was significantly reduced in experimental periodontitis and was further decreased in HFD-PI mice as compared with LFD-PI mice. The inflammation score was significantly higher in HFD-PI mice versus LFD-PI mice, with a concomitant increase in TRAP staining for osteoclast number and area in HFD-PI mice over LFD-PI mice. These data support the concept that M-MDSC expansion during obesity to become osteoclasts during periodontitis is related to increased alveolar bone destruction, providing a more detailed mechanistic appreciation of the interconnection between obesity and periodontitis.
A dosimetry model of refractory ceramic fibers in the hamster lung has been developed based upon the data from recent exposure and recovery experiments conducted by the Research and Consulting Company in Geneva, Switzerland. The modeling results of hamsters showed significant differences from those of an earlier study in rats regarding deposition and clearance of these fibers in the lung. Despite smaller airway size of hamsters, alveolar deposition per breathing cycle in the hamster was found to be higher than that in the rat due to the higher upper airway deposition in rats. The calculated mean deposited fiber size was found to be larger in the hamster, and there were more thin and long fibers deposited in the hamster lung. It was also found that alveolar clearance of refractory ceramic fibers was faster in the hamster. The clearance rate in the hamster did not appear to be fiber size dependent but it varied with lung burden. The higher clearance rate in the hamster resulted in a lower fiber accumulation per unit weight of lung after a long period of exposure. The results of the dosimetry model presented here may contribute to an explanation of different tumorigenic responses observed in the hamster and rat.Recent exposure experiments have shown that hamsters and rats have different tumorigenic responses to kaolin refractory ceramic fibers (RCF) of the same concentration Mast et al., 1994). W h e n these animals inhaled at an exposure concentration of 30 mg/m3, the maximum tolerated dose, 42% of the exposed hamsters developed mesothe-
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.