Fig. 2.

The pyroptosis related to the osteoclasts 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. Signals from bone matrix [66], exosomes from derived MSCs [67], glyburide [71], and MCC950 [67, 68] have been developed in the presented pathway targeting NLRP3. Meanwhile, RANKL, IL-1β, and Smad3 are also the target of action to be regulated to affect bone loss involved in pyroptosis, which can be modulated by Aa [74], UA [75], Auranofin [76] or Alendronate [77], respectively. 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