Mechanical stress abnormalities promote chondrocyte senescence - The pathogenesis of knee osteoarthritis

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115552 - 115552

Published: Sept. 23, 2023

Knee osteoarthritis (KOA) is a common chronic disease in orthopedics, which brings great pain to patients' life and spirit. Therefore, it necessary elucidate the pathogenesis of KOA. The pathophysiology KOA has been linked numerous factors, including oxidative stress, apoptosis, cellular senescence, mitochondrial dysfunction, inflammatory factors. Cellular senescence grown importance as topic study for age-related illnesses recently. also discovered be closely related human aging, process chondrocyte may crucial. Numerous researches have looked at from perspectives mechanical stress abnormalities, overexpression, dysfunction. Many studies that primary overexpression death brought on by an imbalance joint microenvironment. And abnormal initiating cause inflammation, disorders. However, few findings reported literature relationship between these especially senescence. This time, order better understand identify potential connections microenvironments KOA, well dysfunction microenvironmental dysfunctions, we will use starting point. allow us develop new therapeutic approaches

Language: Английский

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Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2

Heliyon, Journal Year: 2023, Volume and Issue: 9(10), P. e20163 - e20163

Published: Sept. 21, 2023

Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis chondrocytes OA unknown. This study aimed to investigate protective potential mechanism curcumin induced by erastin, inducer. CCK-8 assays were used assess viability mouse primary treated 3.33 μM erastin alone or combination different doses curcumin. Various parameters detected, including LDH, SOD, GSH-PX, MDA, ROS Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, FTH1, examined using immunofluorescence western blotting. Nrf2 was knocked down siRNA explore molecular through which protects from erastin-induced ferroptosis. In model knee intracavity injection 10 μL (5 mg/mL), HE staining, Safranin O-Fast Green immunohistochemistry employed evaluate articular cartilage injury. results demonstrated that significantly suppressed expression FTH1 while upregulating levels ROS, TFR1 chondrocytes. Moreover, chondrocyte production reversed Additionally, upregulated level gene protein. Silencing animal experiments, silencing counteracted impact damage tissue vivo, leading significant inhibition progression. Taken together, these findings suggest can inhibit activating signaling pathway, providing further insight into regulatory supporting therapeutic use treatment.

Language: Английский

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Sodium butyrate induces ferroptosis in endometrial cancer cells via the RBM3/SLC7A11 axis

APOPTOSIS, Journal Year: 2023, Volume and Issue: 28(7-8), P. 1168 - 1183

Published: May 11, 2023

Language: Английский

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The Role of Ferroptosis in the Pathogenesis of Osteoarthritis

The Journal of Membrane Biology, Journal Year: 2023, Volume and Issue: 256(3), P. 223 - 228

Published: March 15, 2023

Language: Английский

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The mechanosensitive Piezo1 channel exacerbates myocardial ischaemia/reperfusion injury by activating caspase-8-mediated PANoptosis

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 139, P. 112664 - 112664

Published: July 14, 2024

Language: Английский

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The interplay between biochemical mediators and mechanotransduction in chondrocytes: Unravelling the differential responses in primary knee osteoarthritis

Physics of Life Reviews, Journal Year: 2024, Volume and Issue: 48, P. 205 - 221

Published: Feb. 12, 2024

In primary or idiopathic osteoarthritis (OA), it is unclear which factors trigger the shift of articular chondrocyte activity from pro-anabolic to pro-catabolic. fact, there a controversy about aetiology OA, either mechanical inflammatory. Chondrocytes are mechanosensitive cells, that integrate stimuli into cellular responses in process known as mechanotransduction. Mechanotransduction occurs thanks activation mechanosensors, set specialized proteins convert physical cues intracellular signalling cascades. Moderate levels loads maintain normal tissue function and have anti-inflammatory effects. contrast, over- under-loading might lead cartilage destruction increased expression pro-inflammatory cytokines. Simultaneously, mechanotransduction processes can regulate be regulated by pro- soluble mediators, both local (cells same joint, i.e., chondrocytes themselves, infiltrating macrophages, fibroblasts osteoclasts) systemic (from other tissues, e.g., adipokines). Thus, complex altered so cartilage-preserving adopt different sensitivity signals, mechanic positively transduced healthy may become deleterious under OA conditions. This review aims provide an overview how biochemical exposome alter important these cells. Four principal integrins, Ca2+ channels, cilium Wnt (canonical non-canonical) were targeted. For each brief summary response conditions followed concise published works focus on further regulation pathways factors. conclusion, this paper discusses explores biological mediators influence differential behaviour OA.

Language: Английский

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Piezo1 and its inhibitors: Overview and perspectives

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 273, P. 116502 - 116502

Published: May 14, 2024

The cation channel Piezo1, a crucial mechanotransducer found in various organs and tissues, has gained considerable attention as therapeutic target recent years. Following this trend, several Piezo1 inhibitors have been discovered studied for potential pharmacological properties. This review provides an overview of the structural functional importance well discussing biological activities based on their mechanism action. compounds addressed include toxin GsMTx4, Aβ peptides, certain fatty acids, ruthenium red gadolinium, Dooku1, natural products tubeimoside I, salvianolic acid B, jatrorrhzine, escin. findings revealed that misexpression can be associated with number chronic diseases, including hypertension, cancer, hemolytic anemia. Consequently, inhibiting subsequent calcium influx beneficial effects pathological processes, shown by many vitro vivo studies. However, development is still its beginnings, opportunities challenges remaining to explored.

Language: Английский

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Quercetin Modulates Ferroptosis via the SIRT1/Nrf−2/HO−1 Pathway and Attenuates Cartilage Destruction in an Osteoarthritis Rat Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7461 - 7461

Published: July 7, 2024

Osteoarthritis (OA) is the most common joint disease, causing symptoms such as pain, swelling, and deformity, which severely affect patients' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating development safe effective drugs. Quercetin (QUE), a natural flavonoid widely found fruits vegetables, shows promise due to its broad range pharmacological effects, particularly various degenerative diseases. However, role preventing progression underlying mechanisms remain unclear. In this study, we demonstrated that QUE has protective effect against both vivo vitro, elucidated molecular mechanisms. inhibited expression IL-1β-induced chondrocyte matrix metalloproteinases (MMP3 MMP13) inflammatory mediators INOS COX-2. It also promoted collagen II, thereby extracellular (ECM). Mechanistically, exerts on chondrocytes by activating SIRT1/Nrf-2/HO-1 inhibiting ferroptosis. Similarly, an rat model induced anterior cruciate ligament transection (ACLT), treatment improved articular cartilage damage, reduced normalized abnormal subchondral bone remodeling. serum IL-1β, TNF-α, MMP3, CTX-II, COMP, slowing OA. chondroprotective effects oxidative damage ferroptosis through pathway, effectively alleviating rats.

Language: Английский

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Membrane Dynamics and Cation Handling in Ferroptosis

Physiology, Journal Year: 2024, Volume and Issue: 39(2), P. 73 - 87

Published: Jan. 9, 2024

Ferroptosis, a regulated cell death hallmarked by excessive lipid peroxidation, is implicated in various (patho)physiological contexts. During ferroptosis, peroxidation leads to diverse change membrane properties and the dysregulation of ion homeostasis via cation channels, ultimately resulting plasma rupture. This review illuminates cellular dynamics handling ferroptosis regulation.

Language: Английский

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Ferroptosis: A New Pathway in the Interaction between Gut Microbiota and Multiple Sclerosis

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 6, 2025

Multiple sclerosis (MS) is a chronic autoimmune disorder marked by neuroinflammation, demyelination, and neuronal damage. Recent advancements highlight novel interaction between iron-dependent cell death, known as ferroptosis, gut microbiota, which may significantly influences the pathophysiology of MS. Ferroptosis, driven lipid peroxidation tightly linked to iron metabolism, pivotal contributor oxidative stress observed in Concurrently, affect systemic immunity neurological health, emerges an important regulator homeostasis inflammatory responses, thereby influencing ferroptotic pathways. This review investigates how microbiota dysbiosis ferroptosis impact MS, emphasizing their potential therapeutic targets. Through integrated examination mechanistic pathways clinical evidence, we discuss targeting these interactions could lead interventions that not only modulate disease progression but also offer personalized treatment strategies based on profiling. synthesis aims at deepening insights into microbial contributions implications setting stage for future research exploration.

Language: Английский

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