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Lipoxin A4 (LXA4) has been identified as the braking signal of inflammation, but the specific role of LXA4 in regulating the regenerative potential of periodontal ligament stem cells (PDLSCs) remains unclear. The aim of this study was to investigate whether and, if so, how LXA4 improves the osteogenic differentiation of PDLSCs in a lipopolysaccharide (LPS)‐induced inflammatory environment. We detected the effects of LXA4 on the osteogenic differentiation of PDLSCs in vitro and explored the bone regenerative potential of LXA4‐treated inflammatory PDLSCs in vivo using a calvarial critical sized defect model in male rats. RNA sequencing, real‐time PCR and western blot were performed to elucidate the relevant potential mechanisms. Results showed that LXA4 promoted the proliferation, migration and osteogenic differentiation of PDLSCs in vitro, and effectively improved the impaired osteogenic capacity of PDLSCs induced by LPS both in vitro and in vivo. Mechanistically, LXA4 significantly promoted the PI3K/AKT phosphorylation under inflammatory conditions. Additionally, LY294002 (a PI3K inhibitor) blocked the effect of LXA4, suggesting that the PI3K/AKT pathway is a key signaling pathway that mediates the effect of LXA4 on the osteogenesis of inflammatory PDLSCs. These findings indicate LXA4 may be a promising strategy for periodontal regeneration using inflammatory PDLSCs. [ABSTRACT FROM AUTHOR]

Genetic variation is considered to affect the N6‐methyladenosine (m6A) RNA transcript modification, which is the most prevalent posttranscriptional messenger RNA modification. This study aimed to identify m6A‐associated single‐nucleotide polymorphisms (m6A‐SNPs) that may affect m6A methylation from numerous periodontitis (PD) SNPs. We identified an abundance of m6A‐SNPs by analyzing raw data of published PD genome‐wide association studies and m6A‐SNPs list from the m6AVar database. Other evidence was found in public databases for expression quantitative trait loci (eQTL) and differential gene expression analysis. Accordingly, 1938 m6A‐SNPs were identified, 104 of which appeared to be associated with PD (p < .05) while 65 showed eQTL signals. Lastly, the leading SNP rs2723183 (p = 3.93E−07) was predicted to regulate local gene IL‐37 expression in PD (p = 2.64E−05; in GSE10334) and change regulatory motif RXRA. In summary, dozens of PD‐associated m6A‐SNPs were identified and their possible functions were demonstrated in this study. [ABSTRACT FROM AUTHOR]