Fig.4.

Different targets of action are regulated to affect the pyroptosis related to the macrophages in the process of bone loss. 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. MARK4 [117], mycoplasma salivarium [118], staphylococcus aureus [119], and porphyromonas gingivalis [116] have been found in the presented pathway positively targeting NLRP3 to facilitate pyroptosis, yet glyburide [120], dioscin [91], metformin [121], resveratrol [122] target to suppress NLRP3. Meanwhile, caspase-1 is also the target of action to be modulated by P2X7/AMPK/cyclic stretch [124, 125] and DEX [126], cranberry PACs [127], affecting bone loss involved in pyroptosis. And NF-κB signaling is repressed by PUN [128] and cyclic stretch induced exosomes from human PDLCs [129]. The factors that promote pyroptosis are indicated in green and pyroptosis-suppressor factors are indicated in pink