PGC-1α inhibits NLRP3 signaling through transcriptional activation of POP1 to alleviate inflammation and strengthen osteogenic differentiation of lipopolysaccharide-induced human periodontal stem cells

Periodontitis is a chronic infectious disease that affects the oral health of adults. Periodontal stem cells (PDLSCs) have good self-renewal and multipotential differentiation abilities to maintain the integrity of periodontal support structure and repair defects. This study aimed to elucidate the role of peroxisome proliferator activated receptor-gamma co-activator 1-alpha (PGC-1 alpha) in lipopolysaccharide (LPS)-induced PDLSCs and the underlying mechanisms related to predicated that pyrin domain (PYD)-only protein 1 (POP1). Notably downregulated PGC-1 alpha and POP1 expression was observed in LPS-induced PDLSCs. PGC-1 alpha or POP1 overexpression significantly reduced the inflammation and enhanced the osteogenic differentiation of LPS-treated PDLSCs. Particularly, PGC-1 bound to POP1 promoter region and upregulated POP1 expression. Moreover, POP1 knockdown ameliorated the impacts of PGC-1 alpha overexpression on the inflammation and osteogenic differentiation in LPS-induced PDLSCs. Besides, PGC-1 alpha inactivated NLRP3 signaling in LPS-treated PDLSCs, which was reversed by POP1 knockdown. Taken together, PGC-1 alpha inhibits NLRP3 signaling through transcriptional activation of POP1, thereby alleviating inflammation and strengthening osteogenic differentiation of LPS-induced PDLSCs.