Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes.
Wagener NeleSebastian HardtMatthias PumbergerFriederike SchömigPublished in: Journal of clinical medicine (2024)
(1) Background: Around 50% of hemophilia patients develop severe arthropathy, with even subclinical hemorrhage in childhood potentially leading to intra-articular iron deposition, synovia proliferation, neoangiogenesis, and eventual damage to articular cartilage and subchondral bone. Treatments typically include coagulation factor substitution, radiosynoviorthesis, and joint replacement for advanced cases. This study aims to elucidate programmed cell death mechanisms in hemophilic arthropathy (HA) to identify novel treatments. (2) Methods: Human chondrocytes were exposed to lysed/non-lysed erythrocytes, ferroptosis inducer ML-162, cytokines (IL-1ß, TNFα), and ferric citrate, then assessed for metabolic activity, DNA content, and cell death using Alamar Blue, cyQUANT, and Sytox assays. Three-dimensional spheroids served as a cartilage model to study the effects of erythrocytes and ML-162. (3) Results: Erythrocytes caused significant cell death in 2D cultures ( p < 0.001) and damaged 3D chondrocyte spheroids. Iron citrate and erythrocytes reduced chondrocyte DNA content ( p < 0.001). The ferroptosis pathway was implicated in cell death, with no effects from apoptosis and necroptosis inhibitors. (4) Conclusions: This study offers insights into HA's cell death pathway, suggesting ferroptosis inhibitors as potential therapies. Further studies are needed to evaluate their efficacy against the chronic effects of HA.
Keyphrases
- cell death
- cell cycle arrest
- endothelial cells
- oxidative stress
- end stage renal disease
- extracellular matrix
- signaling pathway
- chronic kidney disease
- rheumatoid arthritis
- single molecule
- cell free
- early onset
- pluripotent stem cells
- single cell
- high throughput
- risk assessment
- young adults
- climate change
- peritoneal dialysis
- human health
- drug induced
- prognostic factors
- bone loss