# Effect of Blood on Synovial Joint Tissues: Potential Role of Ferroptosis
## 4 In Vitro Models
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\begin{tabular}{|c|c|c|} \hline  & **Reference** & **Experimental Design** & **Research Findings** \\ \hline  & & Gene expression and & No significant differences observed in \\  & & biochemical analysis of rabbit & collagen content between ACLT and \\  & & acid analysis of rabbit & control. Significant decrease in GAG \\  & & cartilage following & content observed in cartilage of ACLT in \\  & & intra-articular DEX & comparison to control. Avidin-DEX \\  & & administration in a rabbit ACL & treatment suppressed catabolic gene \\  & & transection model [75] & expression and joint swelling significantly \\  & & more than free DEX treatment [75]. \\ \hline  & & Simulate inflammation and iron & Under inflammation and iron overload, \\  & & overload via administration of & chondrocytes undergo ferroptosis. \\  & & IL-1\(\beta\) and ferric ammonium & Ferroptic induction via erastiu caused \\  & & citrate [76] & increased cartilage degradation enzymes \\  & & & and decreased collagen II expression [76]. \\ \hline  & & Markers of tissue breakdown were \\  & & observed in cartilage constructs without \\  & & Co-culture of human & parallel losses in DNA. Dose-dependent \\  & & chondrocyte-based tissue & loss of viability observed in chondrocyte \\  & & engineered cartilage and human & monolayers, with greater toxicity observed \\  & & chondrocyte monolayer with & with lysates; intact RBCs induced changes \\  & & intact RBC and RBC lysates [11] & to lipid profiles and upregulated highly \\  & & oxidizable fatty acids; RBC lysates induced \\  & & cell death via ferroptosis [11] \\ \hline  & & Assess ferritin formation by & Findings suggest that synovial cells release \\  & & synovial cells exposed to & iron from hemoglobin thereby synthesizing \\  & & hemoglobin [47] & apoferritin without other cell \\  & & hemoglobin [47] & intervention [47] \\ \hline  & & After 4 days of blood exposure, synovial \\  & & & tissue had no significant catabolic activity. \\  & & & After 16 days, synovial tissue had \\  & & & significant cartilage destructive properties. \\  & & & The supernatant of synovial tissue \\  & & & decreased total proteoglycan content and \\  & & & lowered proteoglycan synthesis [24]. \\ \hline  & & & Stromal cell-derived factor-1 (SDF-1) and \\  & & & MMP13 synovial fluid concentration were \\  & & fluid of PTOA guinea pig & statistically similar between idiopathic and \\  & & model [69] & PTOA groups suggesting that other \\  & & inflammatory factors may be involved [69] \\ \hline  & & & Dilution of blood with SF decreased \\  & & & mechanical stiffness of the final clot \\  & & coagulation and mechanical & structure, altered coagulation torque profile \\  & & properties of blood and synovial & over time, and increased fluid permeability. \\  & & fluid mixtures [77] & In comparison to control, SF had a lesser \\  & & effect on mechanical properties of clot \\  & & & possibly due to presence of HA [77] \\ \hline  & & & Synovial inflammation increased 24 h after \\  & & & drug-induced synovitis. Increase of \\  & & and angiogenesis as a result of & macrophage infiltration and endothelial \\  & & & cell proliferation confirmed synovitis and \\  & & model [78] & angiogenesis after meniscal transection. \\  & & & Anti-inflammatory drugs inhibited \\  & & synovitis and synovial angiogenesis [78]. \\ \hline  & & Investigation of solute transport \\  & & measures in bovine & NO and hyaluronic acid (HA) secretion of \\  & & engineered synovium was similar to native \\  & & tissue-engineered synovium & synovial tissue. IL-treated engineered \\  & & & synovium displayed characteristics of \\  & & human OA synovium [79]. \\ \hline \end{tabular}
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Table 1: _Cont._