TABLE 1.

Cellular and molecular mechanisms underlying the interplay between iron overload and OA.

Osteoarthritic phenotypes	Cells	Mechanisms	References
Cartilage degradation	Chondrocytes	Promote lipid peroxidation and stimulate ferroptosis	Sun et al. (2020)
		Mediate mitochondrial dysfunction through ROS production and oxidative stress response	Jing et al. (2021a)
Subchondral bone destruction	Osteoclasts	Promote mitochondrial respiration and oxidative stress, and thus facilitate osteoclast differentiation	Ishii et al. (2009)
		Facilitate osteoclastogenesis by promoting the secretion of apoptotic osteocyte-derived RANKL	Yang et al. (2020)
	Osteoblasts	Inhibit osteogenic differentiation of BMSCs through ROS-mediated Runx2 suppression	Jing et al. (2019)
		Induce osteoblast autophagy and apoptosis by upregulating the level of DMT1	Liu et al. (2017)
		Promote osteoblast apoptosis by inducing ROS production and oxidative stress injury	He et al. (2013)
		Lead to G1 phase arrest and autophagy by inhibiting PI3K/AKT and JAK/STAT3 signaling and promoting p38 signaling	Cen et al. (2018)
Synovitis	Macrophages	Induce M1 polarization by increasing ROS-stimulated p300/CBP acetyltransferase activity and p53 acetylation	Zhou et al. (2018)
	Neutrophils	Promote the accumulation of neutrophils and regulate matrix-degrading enzymes production	Heiland et al. (2010)
	Fibroblast-like synoviocytes	Promote cell proliferation by activating key genes c-myc and mdm2	Hakobyan et al. (2004)