LncRNA AC025580.2 mediates the senescence of periodontal ligament stem cells in inflammatory environments via the alternative splicing of TP53BP1

Periodontal ligament stem cells (PDLSCs) are key cells that suppress periodontal damage during both the progression and recovery stages of periodontitis. Although substantial evidence has demonstrated that incubation under an inflammatory condition may accelerate senescence of PDLSCs, whether such cellular senescence contributes to inflammation-induced cell changes however remains unexplored. In this study, we first observed PDLSC senescence in periodontitis based on comparisons of matched patients, and this cellular senescence was demonstrated in healthy cells that were subjected to inflammatory conditions. We subsequently designed further experiments to investigate the possible mechanism underlying inflammation-induced PDLSC senescence with a particular focus on the role of long noncoding RNAs (lncRNAs). LncRNA microarray analysis and functional gain/loss studies revealed AC025580.2 as a regulator of inflammation-mediated PDLSC senescence. By full-length transcriptome sequencing, we found that overexpressed AC025580.2 interacted with SRSF3 to promote the alternative splicing (AS) of TP53BP1, leading to the upregulation of the TP53BP1-204 transcript. Further functional studies showed that decreased expression of TP53BP1-204 reversed PDLSC senescence, and AC025580.2 overexpression-induced PDLSC senescence was abolished by TP53BP1-204 knockdown. Our data suggest for the first time that LncRNA AC025580.2 plays a key role in regulating PDLSC senescence in inflammatory environments by modulating the AS of TP53BP1. PDLSCs were cultured in normal medium (H-PDLSCs) or in medium containing inflammatory cytokines (I-PDLSCs) . lncRNA expression data from PDLSC