Generation of a p21 Reporter Mouse and Its Use to Identify and Eliminate p21high Cells In Vivo.

P21 and p16 have been identified as inducers of senescence. Many transgenic mouse models have been developed to target cells expressing high levels of p16Ink4a (p16high) and investigate their potential contribution to tissue dysfunction in aging, obesity, and other pathological conditions. However, the specific roles of p21 in various senescence-driven processes remain unclear. To gain a deeper understanding of p21, we built a p21-3MR mouse model containing a p21 promoter-driven module that allowed us to target cells with high p21Chip expression (p21high). Using this transgenic mouse, we monitored, imaged, and eliminated p21high cells in vivo. We also applied this system to chemically induced weakness and found that the clearance of p21high cells improved doxorubicin (DOXO)-induced multi-organ toxicity in mice. By recognizing p21 transcriptional activation spatially and temporally, the p21-3MR mouse model can be a valuable and powerful tool for studying p21high cells to further understand senescence biology.

Quercetin Prevents Oxidative Stress-Induced Injury of Periodontal Ligament Cells and Alveolar Bone Loss in Periodontitis.

PURPOSE: Emerging evidence has indicated that oxidative stress (OS) contributes to periodontitis. Periodontal ligament cells (PDLCs) are important for the regeneration of periodontal tissue. Quercetin, which is extracted from fruits and vegetables, has strong antioxidant capabilities. However, whether and how quercetin affects oxidative damage in PDLCs during periodontitis remains unknown. The aim of this study was to assess the effects of quercetin on oxidative damage in PDLCs and alveolar bone loss in periodontitis and underlying mechanisms. MATERIALS AND METHODS: The tissue block culture method was used to extract human PDLCs (hPDLCs). First, a cell counting kit 8 (CCK-8) assay was used to identify the optimal concentrations of hydrogen peroxide (H2O2) and quercetin. Subsequently, a 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe, RT-qPCR, Western blotting and other methods were used to explore the effects of quercetin on OS in hPDLCs and the underlying mechanism. Finally, quercetin was administered to mice with periodontitis through gavage, and the effect of quercetin on the level of OS and alveolar bone resorption in these mice was observed by immunofluorescence, microcomputed tomography (micro-CT), hematoxylin and eosin staining (H&E) staining and so on. RESULTS: Quercetin at 5 µM strongly activated NF-E2-related factor 2 (NRF2) signaling, alleviated oxidative damage and enhanced the antioxidant capacity of hPDLCs. In addition, quercetin reduced cellular senescence and protected the osteogenic ability of hPDLCs. Finally, quercetin activated NRF2 signaling in the periodontal ligaments, reduced the OS level of mice with periodontitis, and slowed the absorption of alveolar bone in vivo. CONCLUSION: Quercetin can increase the antioxidant capacity of PDLCs and reduce OS damage by activating the NRF2 signaling pathway, which alleviates alveolar bone loss in periodontitis.