Abstract: Objective To explore the mechanism of nucleotide binding oligomerization domain-like receptor protein 3 （NLRP3）/cysteine aspartate specific proteinase-1（Caspase-1） pathway on osteoblast pyroptosis by regulating the level of Caspase-1. Methods Mouse embryonic MC3T3-E1 osteoblasts were cultured and divided into group A with high sugar treatment, group B with high sugar + Caspase-1 inhibitor treatment, group C with high sugar + Caspase-1 siRNA treatment, and control group. The level of lactate dehydrogenase （LDH） released from osteoblasts was detected by light absorption method, the osteoblast pyroptosis was detected by Hoechst33342/PI staining, and the NLRP3, Caspase-1, interleukin-1β （IL-1β）, and IL-18 of osteoblasts were detected by RT-PCR and Western blot respectively. Results The pyroptosis ratio and LDH activity of MC3T3-E1 osteoblasts in group A, B, and C were significantly higher than those in the control group, while those in group B and C were significantly lower than those in group A （P<0.05）. The relative expression levels of NLRP3, Caspase-1, IL-1 β, and IL-18 mRNA and protein in group A, B, and C were higher than those in the control group, while the relative expression levels of Caspase-1, IL-1 β, and IL-18 mRNA and protein in group B and C were significantly lower than those in group A （P<0.05）. There was no significant difference in the relative expression levels of NLRP3 mRNA and protein among group A, B, and C （P>0.05）. Conclusion Inhibition of Caspase-1 inhibits the elevation of IL-1β and IL-18 caused by the elevation of NLRP3 in osteoblasts due to high glucose, thus inhibiting osteoblast pyroptosis.

Key words: Osteoblast, Pyroptosis, Caspase-1, NLRP3/Caspase-1 pathway, Caspase-1 inhibitor, NLRP3 inflammasome