Ferroptosis: a new target for iron overload-induced hemophilic arthropathy synovitis

Han, Zhiwei; Zheng, Liujie; Luo, Dasheng; Pang, Nanyu; Yao, Yunfeng

doi:10.1007/s00277-023-05190-w

Cited by 6 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And it is crucial that iron homeostasis is essential for joint health, and joint iron overload has been shown to be closely related to the pathogenesis of OA ( 206 ). What’s more, the excess iron ions can induce membrane lipid peroxidation and cellular damage in the articular cells via the Fenton reaction ( 204 , 207 ). Recent studies have shown that nuclear receptor coactivator 4 (NCOA4) can exacerbate OA by promoting ferritin autophagy-induced chondrocyte ferroptosis ( 208 ).…”

Section: The Regulated Programmed Cell Death and Glycolysismentioning

confidence: 99%

Glycolysis: an emerging regulator of osteoarthritis

Jiang,

Guo,

Liu

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Osteoarthritis (OA) has been a leading cause of disability in the elderly and there remains a lack of effective therapeutic approaches as the mechanisms of pathogenesis and progression have yet to be elucidated. As OA progresses, cellular metabolic profiles and energy production are altered, and emerging metabolic reprogramming highlights the importance of specific metabolic pathways in disease progression. As a crucial part of glucose metabolism, glycolysis bridges metabolic and inflammatory dysfunctions. Moreover, the glycolytic pathway is involved in different areas of metabolism and inflammation, and is associated with a variety of transcription factors. To date, it has not been fully elucidated whether the changes in the glycolytic pathway and its associated key enzymes are associated with the onset or progression of OA. This review summarizes the important role of glycolysis in mediating cellular metabolic reprogramming in OA and its role in inducing tissue inflammation and injury, with the aim of providing further insights into its pathological functions and proposing new targets for the treatment of OA.

show abstract

Section: The Regulated Programmed Cell Death and Glycolysismentioning

confidence: 99%

Glycolysis: an emerging regulator of osteoarthritis

Jiang,

Guo,

Liu

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Fibroblasts are a type of connective tissue cell and play essential roles in maintaining tissue structure, wound healing, and tissue repair. The induction of ferroptosis in fibroblasts has significant implications for various biological processes and pathological conditions, including tissue homeostasis, tissue fibrosis, wound healing, oxidative stress, and therapeutic interventions in the tumor microenvironment 32 - 38 , thus making it a topic of intense interest in cell biology and biomedical research.…”

Section: Introductionmentioning

confidence: 99%

Translational Potential of Baicalein in Mitigating RSL3-Induced Ferroptosis in Fibroblasts: Implications for Therapeutic Interventions

Kuo,

Rau,

et al. 2024

Int. J. Med. Sci.

View full text Add to dashboard Cite

Background: Ferroptosis is an iron-driven cell-death mechanism that plays a central role in various diseases. Recent studies have suggested that baicalein inhibits ferroptosis, making it a promising therapeutic candidate. Materials and Methods: Fibroblast cultures were treated with different agents to determine the effects of baicalein on ferroptosis. Ferroptosis-related gene expression, lipid peroxidation, and post-treatment cellular structural changes were measured using real-time quantitative polymerase chain reaction, C11-BODIPY dye, and transmission electron microscopy, respectively. Results: Baicalein significantly inhibited rat sarcoma virus selective lethal 3-induced ferroptosis in fibroblasts. Moreover, in baicalein-treated groups, reduced ferroptosis-related gene expression, decreased lipid peroxidation, and maintained cell structure was observed when compared with those of the controls. Discussion: The ability of baicalein to counteract RSL3-induced ferroptosis underscores its potential protective effects, especially in diseases characterized by oxidative stress and iron overload in fibroblasts. Conclusion: Baicalein may serve as a potent therapeutic agent against conditions in which ferroptosis is harmful. The compound's efficacy in halting RSL3-triggered ferroptosis in fibroblasts paves the way for further in vivo experiments and clinical trials.

show abstract

“…Recent studies have highlighted the complexity of HA, emphasizing the role of recurrent hemarthrosis in inducing synovial hyperplasia, and the production of proinflammatory cytokines such as TNF-alpha, interleukin-6, and 1-beta. These cytokines amplify fibroblast-like synoviocyte proliferation and the production of reactive oxygen species that induce chondrocyte apoptosis, inevitably leading to osteochondral damage due to the direct exposure of chondrocytes to iron, metalloproteinases, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) produced by fibroblast-like synoviocytes when stimulated by inflammation [3,5].…”

Section: Introductionmentioning

confidence: 99%

Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes

Wagener,

Hardt,

Pumberger

et al. 2024

JCM

View full text Add to dashboard Cite

(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.

show abstract

Ferroptosis: a new target for iron overload-induced hemophilic arthropathy synovitis

Cited by 6 publications

References 36 publications

Glycolysis: an emerging regulator of osteoarthritis

Glycolysis: an emerging regulator of osteoarthritis

Translational Potential of Baicalein in Mitigating RSL3-Induced Ferroptosis in Fibroblasts: Implications for Therapeutic Interventions

Cartilage Destruction by Hemophilic Arthropathy Can Be Prevented by Inhibition of the Ferroptosis Pathway in Human Chondrocytes

Contact Info

Product

Resources

About