Table 1.
Evidence of ferroptosis in inflammatory arthritis.
| Disease | Model | Evidence of Ferroptosis | |
|---|---|---|---|
| Evidence of iron accumulation | Evidence of lipid peroxidation/oxidative stress | ||
| RA | Patient | 1. Iron deposited in synovium (35) 2. FTH, FLH, and DMT1 were positive in FLSs and macrophages; TfR were positive in FLSs (36) 3. sTfR increased, iron decreased in serum (37) 4. Iron increased, TfR1 and NCOA4 increased, Nrf2 decreased in LPS-treated synoviocytes (38) 5. Iron increased in the synovial fluid of patients with high disease activity compared with patients with moderate disease activity (39). |
1. MitoROS increased in blood and monocytes (20) 2. GSH and GPx decreased in blood (40) 3. MDA increased in blood, RBC and synovial fluid; TBARS increased in blood; F2-I increased in plasma; MAA adducts increased in synovium (20, 39); 4. MDA increased, GPX4, SLC7A11 and SLC3A2L decreased in LPS-treated synoviocytes (38) 5. 4-HNE increased in the hyperplastic synovium of RA patients compared with OA patients (39). |
| Animal | 1. FTH1 increased in the synovium and FLSs of CIA model mice (41). | 1. 4-HNE increased in the synovium of CIA model mice compared with normal mice (39). 2. ACSL4 decreased, GPX4 and SLC7A11 increased in the synovium and FLSs of CIA model mice (41). |
|
| OA | Patient | 1. Iron increased in synovial fluid (42) 2. Ferritin increased in serum (43) |
1. 4-HNE/protein adduct increased in synovial fluid and osteoblasts (44–47) |
| Animal | 1. TfR1 and DMT1 increased, FPN decreased in OA model mice and in IL-1β-treated or TNF-α-treated chondrocytes (42) 2. MMP-3 and MMP-13 increased, chondrogenic related proteins↓ in FAC-treated chondrocytes (42) 3. Cartilage destruction decreased in DMT1-inhibited OA model mice (42) |
1. GPX4 and SLC7A11 decreased, ROS and ACSL4 increased in IL-1β-treated and FAC-treated chondrocytes, and FER-1 can inhibit these (48) 2. Cartilage degradation decreased, type II collagen increased in the FER-1-treated OA model mice (48) |
|
| AS | Patient | 1. Iron overloaded in PMNs and platelets (49) 2. TfR decreased in serum (50) |
1. TOS and OSI increased, TAS decreased in plasma (51) 2. SOD, CAT, and NO increased in the blood of AS patients with MetS (52) 3. AOPPs and ROS increased in serum (53) |
| Animal | Not known yet. | 1. GPx decreased in serum (54) 2. ROS and MDA increased, GPx activity↓in the connective tissue around the vertebral body (55) |
|
| GA | Patient | 1. Ferritin increased in serum (56) | Not known yet. |
| Animal | Not known yet. | 1. MDA increased, GPx decreased in plasma, liver, and spleen (57) | |
ACSL4, acyl-CoA synthetase long-chain family member 4; AOPPs, oxidative protein products; AS, ankylosing spondylitis; CAT, catalase; CIA, collagen-induced arthritis; DMT1, divalent metal transporter 1; FAC, ferric ammonium citrate; FER-1, ferrostatin-1; F2-I, isoprostane; FLSs, fibroblast-like synoviocytes; FPN, ferroportin; FTH, ferritin heavy chain; FTL, ferritin light chain; FSP1, ferropsis -suppressor-protein 1; GA, gouty arthritis; GPx, glutathione peroxidase; GSH, glutathione; GPX4, glutathione peroxidase 4; 4-HNE, 4-hydroxynonenal; IL-1β, interleukin-1β; LPS, lipopolysaccharide; MAA, malondialdehyde-acetaldehyde; MDA, malonaldehyde; MetS, metabolic syndrome; mitoROS, mitochondrial reactive oxygen species; MMPs, matrix metalloproteinase; NCOA4, nuclear receptor coactivator 4; NO, nitric oxide; Nrf2, nuclear factor erythroid 2-related factor 2; OA, osteoarthritis; OSI, oxidative stress index; PMNs, polymorphonuclear cells; RA, rheumatoid arthritis; ROS, reactive oxygen species; SLC3A2, solute carrier family 3 member 2; SLC7A11, solute carrier family 7 member 11; SOD, markers superoxide dismutase; sTfR, soluble transferrin receptor; TAS, total antioxidant status; TBARS, thiobarbituric acid reactive substances; TfR1, transferrin receptor 1; TNF, tumor necrosis factor; TOS, total oxidative status.