TABLE 3.

Summary of the pathogenesis of osteoarthritis (OA) and the relationship with different types of cell death (Hunter and Bierma-Zeinstra, 2019; An et al., 2020; Riegger and Brenner, 2019; Shi et al., 2019; Royce et al., 2019; Zhou et al., 2021; Yao et al., 2021; Li et al., 2020; Tang et al., 2018; Xu et al., 2019; Sun et al., 2021; Xu L. et al., 2020; Tian et al., 2020; Aluganti Narasimhulu and Singla, 2021; Zu et al., 2019; Zhao Y. et al., 2018).

Osteoarthritis pathogenesis	Cell Death Types
	Pyroptosis	Apoptosis	Necroptosis	Ferroptosis
Increased inflammatory component	IL-1β↑, IL-18↑, Caspase-1↑, NLRP3↑, MMP-1↑, MMP-13↑, NLRP3↑, NLRP1↑	IL-1β↑, IL-6↑, IL-8↑, TNF-α↑, Bax↑, Bcl-2↑, ROS↑, MMP2↑, MMP9↑	MLKL↑, Cleaved caspase8↑, p-MLKL↑	Expression of catabolic genes Mmp3↑, Mmp13↑, Adamts5↑, Ptsg2↑, Col10a1↑
Mechanical overload	IL-1β↑, IL-18↑, Caspase-1↑, NLRP3↑, MMP-1↑, MMP-13↑	Cleaved caspase-3, -6, -7, and -8↑, actin polymerization↑	RIP1↑, RIP3↑, Caspase-8↑, ROS↑, Mitochondrial membrane potential↓	MMP13↑, collagen II↓
Metabolic alterations	Caspase-1↑, IL-1β↑, IL-18↑, Gasdermin-D↑	Phospho-fructose kinase 1 (Pfk1) l↓, hexokinase II (Hk2) l↓, ATP l↓, mitochondrial fusion	Inhibits necroptosis through the hypermethylation of the promoter	Reactive oxygen species (ROS) ↑, lipid ROS↑, MMP13↑, collagen II↓
Cell senescence	IL-1β↑, IL-18↑, activation caspase-1 or caspase-11	COL10A1↑, IL-1↑, TNF-α↑, MMP-13↑, ADAMTS5↑, COL2A1↓	Oxidative stress↑, mTOR signaling↑, DAMPs↑	Mmp3↑, Mmp13↑, Adamts5↑, Ptsg2↑, Col10a1↑