.png){kind=icon}
.png){kind=icon}
Return
Signal-driven interplay between lipid peroxidation and ferroptosis orchestrates osteoarthritis degeneration
.png){kind=icon}
OA
AI
M
J
S
M
M
S
I
E
DOI：10.1016/j.jot.2026.101178.png)
.png){kind=icon}
.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Osteoarthritis (OA) is progressively documented as a whole-joint disorder in which oxidative stress, iron dysregulation and intercellular communication together drive progressive tissue degeneration. Among the chief oxidative mechanisms, lipid peroxidation has arisen as a critical contributor to cartilage destruction and inflammatory signalling cascade. Reactive aldehydes produced during lipid peroxidation, mainly malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), function as electrophilic mediators that change signalling pathways, extracellular matrix components and proteins, including NF-κB and MAPK. Persistent oxidative stress converges on ferroptosis, an iron-dependent form of regulated cell death characterized by impaired GPX4 activity, lipid peroxide accumulation and glutathione depletion. Ferroptotic chondrocytes also amplify osteoarthritic progression by releasing matrix-degrading enzymes and inflammatory cytokines that impact neighbouring osteoclasts, osteoblasts and synoviocytes. Additionally, mechanical stress contributes to this pathological network through Piezo1/TRPV4-mediated mechanotransduction, connecting aberrant biomechanical loading to intracellular calcium imbalance, ferroptosis activation and iron accumulation. Accumulative evidence specifies that dysregulated iron homeostasis plays a dual role in OA pathogenesis, as iron overload promotes reactive oxygen species generation through Fenton chemistry, whereas iron deficiency impairs antioxidant defence and osteogenesis mechanisms. Therapeutically, biomaterial-based nano-delivery systems, antioxidant compounds, iron chelators, and ferroptosis-targeted interventions have confirmed potential in restoring redox balance and suppress OA-associated inflammation. Cerium oxide, selenium, and MnO2 nanozymes, together with smart intra-articular delivery platforms, provide targeted reactive oxygen species scavenging and improve therapeutic localization within inflamed joints. By integrating mechanotransduction, iron metabolism, ferroptosis and lipid peroxidation, inter-tissue communication into a unified mechanistic framework, this review highlights emerging diagnostic biomarkers and translational strategies for the development of disease-modifying therapies in osteoarthritis.
Keywords:
Chondrocyte signalling
Ferroptosis
Iron homeostasis
Lipid peroxidation
Osteoarthritis
Redox signalling
AI Summary
Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.
Journal
IF:
7.8
Papers:
1.1K
Citations:
4.1K
Organization
Cited Papers