Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes
(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 typi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/13/2/559 |
| _version_ | 1797339678150492160 |
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| author | Nele Wagener Sebastian Hardt Matthias Pumberger Friederike Schömig |
| author_facet | Nele Wagener Sebastian Hardt Matthias Pumberger Friederike Schömig |
| author_sort | Nele Wagener |
| collection | DOAJ |
| description | (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 (<i>p</i> < 0.001) and damaged 3D chondrocyte spheroids. Iron citrate and erythrocytes reduced chondrocyte DNA content (<i>p</i> < 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. |
| first_indexed | 2024-03-08T09:51:51Z |
| format | Article |
| id | doaj.art-593adf49113f49d78f6e9c1b51f315d7 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-08T09:51:51Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-593adf49113f49d78f6e9c1b51f315d72024-01-29T14:03:02ZengMDPI AGJournal of Clinical Medicine2077-03832024-01-0113255910.3390/jcm13020559Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human ChondrocytesNele Wagener0Sebastian Hardt1Matthias Pumberger2Friederike Schömig3Center for Musculoskeletal Surgery, Charité-University Medicine Berlin, Charitéplatz 1, 10117 Berlin, GermanyCenter for Musculoskeletal Surgery, Charité-University Medicine Berlin, Charitéplatz 1, 10117 Berlin, GermanyCenter for Musculoskeletal Surgery, Charité-University Medicine Berlin, Charitéplatz 1, 10117 Berlin, GermanyCenter for Musculoskeletal Surgery, Charité-University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany(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 (<i>p</i> < 0.001) and damaged 3D chondrocyte spheroids. Iron citrate and erythrocytes reduced chondrocyte DNA content (<i>p</i> < 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.https://www.mdpi.com/2077-0383/13/2/559hemophilic arthropathyferroptosiscartilage destructionbone defectshemophiliahemarthrosis |
| spellingShingle | Nele Wagener Sebastian Hardt Matthias Pumberger Friederike Schömig Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes Journal of Clinical Medicine hemophilic arthropathy ferroptosis cartilage destruction bone defects hemophilia hemarthrosis |
| title | Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes |
| title_full | Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes |
| title_fullStr | Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes |
| title_full_unstemmed | Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes |
| title_short | Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes |
| title_sort | cartilage destruction by hemophilic arthropathy can be prevented by inhibition of the ferroptosis pathway in human chondrocytes |
| topic | hemophilic arthropathy ferroptosis cartilage destruction bone defects hemophilia hemarthrosis |
| url | https://www.mdpi.com/2077-0383/13/2/559 |
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