Pentraxin-3 Promotes LPS-Induced Pyroptosis in Human Periodontal Ligament Stem Cells.

ABSTRACT

The aim of this study was to explore the function of Pentraxin-3 (PTX3) in cell viability, pyroptosis, inflammation, osteogenic differentiation, and oxidative stress of lipopolysaccharide (LPS)-stimulated human periodontal ligament stem cells (hPDLSCs). In the study, hPDLSCs were stimulated by LPS from Porphyromonas gingivalis to establish an in vitro inflammatory cellular model. Protein expression was measured using Western blotting. mRNA levels were evaluated by qRT-PCR. Cell viability, inflammatory cytokine production, and caspase-1 activity was measured with commercially available kits. Oxidative stress was assessed by examining reactive oxygen species and nitric oxide production. We found that PTX3 was upregulated in LPS-stimulated hPDLSCs. PTX3 overexpression aggravated LPS-induced cell viability loss, inflammatory cytokine production, and oxidative stress, as well as suppressed the osteogenic differentiation in hPDLSCs, while silencing PTX3 had the opposite effects. Further, PTX3 overexpression promoted NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome overactivation and pyroptosis, evidenced by increased protein levels of NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein (ASC), and N-terminal gasdermin D (GSDMD-N). Inhibition of NLRP3 inflammasome and/or caspase-1 partially attenuated the effects of PTX3 on LPS-stimulated hPDLSCs. This study indicated that PTX3 promotes LPS-induced pyroptosis and inflammation in hPDLSCs through activation of the caspase-1-dependent NLRP3 inflammasome.