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) |