Fig.1.

Pyroptosis modulates the activities of osteoclasts, osteoblasts, macrophages, chondrocytes, and periodontal ligament cells to play a non-negligible role in bone loss. In the canonical pathway, after exposure to PAMP and DAMP, NLRP3 inflammasome is activated and followed by the recruitment of ASC and pro-caspase-1, subsequently producing the pro-inflammatory cytokines IL-1β and IL-18. The activation mediated by aging, infection, estrogen deficiency or inflammatory condition of TLR or TNFR prompts NF-kB signaling, causing increased expression of NLRP3, pro-IL-1β, and pro-IL-18. In the noncanonical pathway, caspase-4/-5/-11 is activated upon binding to LPS of Gram-negative bacteria. Caspase-1 and caspase-4/-5/-11 cleave GSDMD into a GSDMD-N-terminal domain which anchors in the cell membrane and results in cell rupture as well as the efflux of K + . In the process of pyroptosis, inflammasomes facilitate osteoclast activities and thus improve the bone resorption ability of osteoclasts. Osteoblasts, chondrocytes, periodontal ligament cells, and macrophages can elevate osteoclast activity in the context of inflammasome activation, meanwhile, the decreased osteoblast activity and increased pyroptosis of osteoblasts and periodontal ligament cells can directly upregulate bone loss and inflammation