Fig.3.

The pyroptosis related to the osteoblasts in the process of bone loss is affected by the regulation on different targets of actions. Exposure to PAMPs or DAMPs and then influenced by NF-κB, the NLRP3 inflammasome complex assemblies and activates caspase-1 and subsequently results in the cleavage of the proinflammatory cytokines IL-1β and IL-18. Caspase-1 and caspase-4/-5/-11 cleave GSDMD into a GSDMD-N-terminal domain that anchors in the cell membrane, leading to the cell rupture. Wnt/β-catenin signaling [98], IL-17 [97], IL-18BP [52], MCC950 [99], TXNIP [89], shRNA [85] and ROS that could be inhibited by N-acetyl-L-cysteine [99], have been developed in the presented pathway targeting NLRP3. Meanwhile, NF-κB, LPS and caspase-1 are also the target of action to be regulated by PKR [103], Necrosulfonamide [102], high glucose [101] or IL-18BP [52], affecting bone loss involved in pyroptosis. The factors that promote pyroptosis are indicated in green and pyroptosis-suppressor factors are indicated in pink as well as factors that can have both effects are indicated in brown