Fig 2: Proposed mechanical models of TNF-α-induced PANoptosis through the NLRP3-PANototome pathway. TNF-α activation induces PANoptosis in differentiating osteoblasts, probably because of the activation of the PANoptosome. Our predicted PANoptosome components present in osteoblasts may be RIPK3, ASC, CASP8, and NLRP3, and when they are activated, massive cell death leads to failure of MC3 T3-E1 induction of osteogenesis

Fig 3: Colocalization and interaction of Caspase8 with ASC, NLRP3, RIPK1, and PIPK3 in MC3 T3-E1 cells. A The localization of CASP8 with ASC, NLRP3, RIPK1, and PIPK3 in MC3 T3-E1 cells (induced to differentiate for 4 d and stimulated with TNF-α for 72 h) as detected by immunofluorescence. B Co-IP was performed using anti-RIPK1 antibody. The effect of RIPK1 under TNF-α stimulation on NLRP3/CASP8/ASC was detected. Components of the PANoptotic complex may contain CASP8, ASC, NLRP3, RIPK1, or PIPK3