RESUMO
The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.
RESUMO
El presente estudio evalúa los resultados de la utilización del fosfato tricálcico beta en la preservación de alvéolos postextracción al emplearlo solo o en conjunto con membranas no reabsorbibles. Se seleccionaron 18 dientes con indicación de extracción y con condiciones favorables para la preservación del alvéolo y posterior colocación de un implante oseointegrado. En 10 alvéolos se utilizó como relleno fosfato tricálcico beta en conjunto con membrana no reabsorbible, y 8 alvéolos fueron tratados solamente con fosfato tricálcico beta. Previo a la cirugía se evaluó el ancho y alto de cada alvéolo, mediante una tomografía computarizada de alta resolución, evaluación que fue repetida 6 meses después de realizada la intervención quirúrgica. Al momento de efectuar la técnica quirúrgica para la instalación de los implantes se tomaron muestras histológicas del sitio de colocación del implante para estudiar las características histológicas del sitio injertado después de 6 meses de realizada la cirugía de extracción dentaria y preservación de alvéolo. El uso de fosfato tricálcico beta, independiente o no del uso de membrana, mantuvo la altura del alvéolo transcurridos 6 meses desde su colocación, mientras que el ancho del alvéolo se mantuvo solo en el grupo sin membrana. Los resultados histológicos demostraron cantidades variables de regeneración ósea.
The present study evaluated the results of the post-extraction socket preservation technique using Beta-Tricalcium Phosphate with and without the use of a non-resorbable membrane. A total of 18 teeth with indication of extraction and socket preservation were selected, with 10 alveoli being treated with Beta-Tricalcium Phosphate combined with a non-resorbable membrane, and the other 8 with Beta-Tricalcium Phosphate only. The width and height of each socket was evaluated using computed tomography, prior to the extraction, and 6 months after the surgery. At the time of performing the surgical technique for installing the implants, histological specimens were taken from the implant site in order to study the graft site 6 months after the dental extraction surgery and alveoli preservation.The use of Beta-Tricalcium Phosphate, whether a membrane is used or not, maintained the alveolar height 6 months after the extraction, while the width of the alveolus only remained in the group without membrane. Histological results showed varying amounts of bone regeneration.