FIGURE 4.

The relationship between necroptosis and osteoarthritis (OA). Necroptosis: Joint trauma leads to the release of death-related triggers including tumor necrosis factor alpha (TNF-α), reactive oxygen/nitrogen species (ROS/RNS), and damage associated molecular patterns (DAMPs). These factors subsequently lead to TNF receptor 1 (TNFR1) activation, forming the TNFR1 complex I and the receptor interacting protein kinase 1 (RIPK1). RIPK1 and RIPK3 interact to activate caspase-8. When caspase8 is inactivated it leads to the appearance of necrosomes which cause the recruitment and phosphorylation of mixed-lineage kinase domain-like protein (MLKL), ultimately leading to disruption of membrane integrity. This leads to the formation of necroptosis.