Use of Micro-CT Imaging to Assess Ventral Mandibular Cortical Thickness and Volume in an Experimental Rodent Model With Chronic High-Phosphorus Intake

Adverse effects of high dietary phosphorus on bone health have been observed in both animal and human studies. The aim of the investigation was to examine chronic effects of high phosphorus diet on the apical mandibular cortical thickness and volume in a hystricomorph rodent (Octodon degus) using microcomputed tomography. Male degus were randomly divided into two groups fed by different mineral contents from the age of 12 weeks till the age of 17 months. The micro-CT scanning and wall thickness analysis were applied on the region of the mandible exactly under the apices of the 4th premolar tooth, first molar tooth, and second molar tooth in two animals from each group. General overview and mapping of the ventral mandibular bone thickness revealed pronounced bony mandibular protrusions in all the animals fed a high-phosphorus diet with obvious bone thinning apically to the 4th premolar and first and second molar tooth apices. Mandibular bone volume and thickness located apically to the premolar and molars were statistically significantly smaller/thinner in the group fed by a high phosphorus diet. The thinnest bone measured 0.004 mm, where the mandibular 4th premolar tooth almost perforated the mandibular cortex. Similar studies of metabolic bone disease and its influence on alveolar bone were also published in rats and mice. The influence of different environmental, infectious, or metabolic factors on the growing tooth, alveolar bone formation, and bone pathologies must be done experimentally on growing animals. In contrast, degus have continuously growing dentition, and the effect of any of the above listed factors can be studied in this animal model at any age and for longer time periods.

SET8，a novel regulator to ameliorate vascular calcification via activating PI3K/Akt mediated anti-apoptotic effects.

Previous studies have showed that the apoptosis of vascular smooth muscle cells (VSMCs) underlies the mechanism of pathological calcifications in patients with chronic kidney disease (CKD). SET domain-containing protein 8 (SET8), as an efficient protein has been reported to modulate cell apoptosis in hepatocellular carcinoma cell, esophageal squamous cell and neuronal cell through regulating pathological processes, such as cell-cycle progression and transcription regulation. However, whether SET8 is involved in high phosphorus induced vascular calcification by mediating apoptosis remains undefined. Here, we reported that SET8 was located both in nucleus and cytoplasm, and significantly downregulated in calcification models. SET8 deficiency promoted the apoptosis of VSMCs, which was indicated by the increased Bax/Bcl-2 and cleaved caspase-3/total caspase-3 ratios. Mechanistically, PI3K/Akt pathway was mediated by SET8 and inhibition of PI3K/Akt signaling pathway by giving LY294002 or transfecting Akt phosphorylation inactivated mutation plasmid increased apoptosis and calcification. Akt phosphorylation constitutively activated mutation could reduce apoptosis and calcification of VSMCs. Furthermore, exogenous overexpression of SET8 could reverse the effect of PI3K/Akt inhibition on the apoptosis and calcification of VSMCs. In summary, our researches suggested that SET8 overexpression ameliorated high phosphorus induced calcification of vascular smooth muscle cells via activating PI3K/Akt mediated anti-apoptotic effects.