Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: Sept. 30, 2023

Abstract During aging and after traumatic injuries, cartilage bone cells are exposed to various pathophysiologic mediators, including reactive oxygen species (ROS), damage-associated molecular patterns, proinflammatory cytokines. This detrimental environment triggers cellular stress subsequent dysfunction, which not only contributes the development of associated diseases, that is, osteoporosis osteoarthritis, but also impairs regenerative processes. To counter ROS-mediated reduce overall tissue damage, possess diverse defense mechanisms. However, antioxidative capacities limited thus ROS accumulation can lead aberrant cell fate decisions, have adverse effects on homeostasis. In this narrative review, we address oxidative as a major driver processes in bone, senescence, misdirected differentiation, death, mitochondrial impaired mitophagy by illustrating consequences homeostasis regeneration. Moreover, elaborate mechanisms, with particular focus response mitophagy, briefly discuss respective therapeutic strategies improve protection.

Language: Английский

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Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 29, 2023

Abstract Osteoarthritis (OA) is a multifactorial and increasingly prevalent degenerative disease that affects the whole joint. The pathogenesis of OA poorly understood there lack therapeutic interventions to reverse pathological process this disease. Accumulating studies have shown overproduction reactive oxygen species (ROS) ROS-induced lipid peroxidation are involved in OA. 4-Hydroxy-2-nonenal (4-HNE) malondialdehyde (MDA) received considerable attention for their role cartilage degeneration subchondral bone remodeling during development. Ferroptosis form cell death characterized by control membrane recent suggested chondrocyte ferroptosis contributes progression. In review, we aim discuss peroxidation-derived 4-HNE MDA progression addition, potential controlling accumulation inhibiting discussed.

Language: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression

Advanced Science, Journal Year: 2023, Volume and Issue: 10(10)

Published: Jan. 22, 2023

Mitochondrial homeostasis is of great importance for cartilage integrity and associated with the progression osteoarthritis (OA); however, underlying mechanisms are unknown. This study aims to investigate role mitochondrial deacetylation reaction mechanistic relationship OA development. Silent mating type information regulation 2 homolog 3 (SIRT3) expression has a negative correlation severity in both human arthritic mice inflammatory chondrocytes. Global SIRT3 deletion accelerates pathological phenotype post-traumatic mice, as evidenced by extracellular matrix collapse, osteophyte formation, synovial macrophage M1 polarization. Mechanistically, prevents targeting deacetylating cytochrome c oxidase subunit 4 isoform (COX4I2) maintain at post-translational level. The activation honokiol restores metabolic equilibrium protects from development OA. Collectively, loss essential OA, whereas SIRT3-mediated proteins COX4I2 rescues OA-impaired respiratory chain functions improve phenotype. Herein, induction provides novel therapeutic candidate treatment.

Language: Английский

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Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, clinical application for capsaicin TRPV1 agonist is largely limited its chronic toxicity. To address this issue, we developed bifunctional controllable magnetothermal switch targeting alleviation OA progression coupling magnetic nanoparticles (MNPs) to monoclonal antibodies (MNPs-TRPV1). Under alternating field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient trigger opening activation TRPV1, effectively impeded chondrocyte This modulation simultaneously attenuated synovitis cartilage degeneration in mice incurred destabilization medial meniscus surgery, indicating delayed progression. Furthermore, with AMF exposure remarkably reduced knee pain sensitivity, alleviated crippled gait, improved spontaneous ambulatory activity performance model. Overall, work provides pathogenesis-based precise therapy temporally spatially manner.

Language: Английский

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Single-cell RNA sequencing in orthopedic research

Bone Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Feb. 24, 2023

Although previous RNA sequencing methods have been widely used in orthopedic research and provided ideas for therapeutic strategies, the specific mechanisms of some disorders, including osteoarthritis, lumbar disc herniation, rheumatoid arthritis, fractures, tendon injuries, spinal cord injury, heterotopic ossification, osteosarcoma, require further elucidation. The emergence single-cell (scRNA-seq) technique has introduced a new era on these topics, as this method provides information regarding cellular heterogeneity, cell subtypes, functions novel subclusters, potential molecular mechanisms, cell-fate transitions, cell‒cell interactions that are involved development diseases. Here, we summarize subpopulations, genes, underlying diseases identified by scRNA-seq, improving our understanding pathology providing insights into approaches.

Language: Английский

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CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 28, 2023

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid and upregulation senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 highly expressed in secondary generation chondrocytes its deficiency can alleviate FASN related senescent phenotypes osteoarthritis progression. impedes proteasome-mediated degradation inhibiting acetylation-mediated ubiquitination. Meanwhile, induces RanBP2-mediated SUMOylation enhances protein stability. CircRREB1-FASN axis inhibits FGF18 FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection adenovirus-CircRreb1 reverses the protective effects CircRreb1 mice. Further therapeutic interventions could have beneficial identifying as potential prognostic target for OA.

Language: Английский

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Near Infrared Responsive Gold Nanorods Attenuate Osteoarthritis Progression by Targeting TRPV1

Advanced Science, Journal Year: 2024, Volume and Issue: 11(16)

Published: Feb. 15, 2024

Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation transient receptor potential vanilloid 1 (TRPV1) significantly alleviated degeneration by abolishing chondrocyte ferroptosis. In this work, in view thermal activated feature TRPV1, Citrate-stabilized gold nanorods (Cit-AuNRs) conjugated to TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) as a photothermal switch for chondrocytes under near infrared (NIR) irradiation. The conjugation barely affect morphology and physicochemical properties Cit-AuNRs. Under NIR irradiation, Cit-AuNRs@Anti-TRPV1 exhibited good biocompatibility flexible responsiveness. Intra-articular injection followed irradiation attenuated degradation suppressing osteophyte formation subchondral bone sclerosis are remarkably NIR-inspired Cit-AuNRs@Anti-TRPV1. Furthermore, evidently improved physical activities pain destabilization medial meniscus (DMM)-induced OA mice. study reveals protects from ferroptosis attenuates progression, providing therapeutic strategy treatment OA.

Language: Английский

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Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155738 - 155738

Published: June 1, 2024

Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, autophagy, characterised by iron, reactive oxygen species, lipid peroxide accumulation, as well glutathione (GSH) depletion GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis the onset progression respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, fibrosis, cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in treatment owing natural properties potential efficacy. These can effectively regulate modulating several key signalling pathways such system Xc

Language: Английский

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