Mechanism of HIFs in osteoarthritis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 20, 2023

Osteoarthritis (OA) is a common disabling disease which has high incidence rate in the elderly. Studies have found that many factors are involved pathogenesis of OA. Hypoxia-inducible (HIFs) core regulators induce hypoxia genes, repair cellular oxygen environment, and play an important role treatment For example, HIF-1α can maintain stability articular cartilage matrix, HIF-2α able to cause chondrocyte apoptosis intensify in-flammatory response, HIF-3α may be target gene HIF-2α, thereby playing negative regulatory role. This review examines mechanism HIFs extracellular matrix degradation, apoptosis, inflammatory reaction, autophagy then further expounds on roles OA, consequently providing theoretical support for OA new treatment.

Language: Английский

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Targeting regulated chondrocyte death in osteoarthritis therapy

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 215, P. 115707 - 115707

Published: July 26, 2023

Language: Английский

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Supramolecular self-assembly of EGCG-selenomethionine nanodrug for treating osteoarthritis

Bioactive Materials, Journal Year: 2023, Volume and Issue: 32, P. 164 - 176

Published: Oct. 9, 2023

Osteoarthritis (OA) has emerged as a significant health concern among the elderly population, with increasing attention paid to ferroptosis-induced OA in recent years. However, prolonged use of nonsteroidal anti-inflammatory drugs or corticosteroids can lead series side effects and limited therapeutic efficacy. This study aimed employ Mannich condensation reaction between epigallocatechin-3-gallate (EGCG) selenomethionine (SeMet) efficiently synthesize polyphenol-based nanodrugs aqueous media for treating OA. Molecular biology experiments demonstrated that EGCG-based (ES NDs) could effectively reduce glutathione peroxidase 4 (GPX4) inactivation, abnormal Fe2+ accumulation, lipid peroxidation induced by oxidative stress, which ameliorated metabolic disorder chondrocytes other multiple pathological processes triggered ferroptosis. Moreover, imaging histopathological analysis destabilization medial meniscus model mice confirmed ES NDs exhibiting relieving The intra-articular delivery represents promising approach joint inflammatory diseases.

Language: Английский

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Specificity protein 1-mediated ACSL4 transcription promoted the osteoarthritis progression through suppressing the ferroptosis of chondrocytes

Journal of Orthopaedic Surgery and Research, Journal Year: 2023, Volume and Issue: 18(1)

Published: March 10, 2023

Abstract Background Chondrocytes are the main cell damage type involved in occurrence and development of osteoarthritis (OA). Ferroptosis has been confirmed to be related many degenerative diseases. This research aimed explore role Sp1 ACSL4 ferroptosis IL-1β-treated human chondrocyte cells line (HCCs). Methods The viability was detected with CCK8 assay. ROS, MDA, GSH, Fe 2+ levels were assessed corresponding detecting kits. Col2a1, Acan, Mmp13, Gpx4 Tfr1 determined by RT-qPCR Western blot conducted evaluate Acsl4 levels. PI staining carried out analyze death. double luciferase report verify interaction between Sp1. Results results showed that IL-1β stimulation elevated LDH release, viability, MDA declined GSH HCCs. Additionally, mRNA prominently decreased, while Mmp13 stimulated Furthermore, protein upregulated IL-1β-stimulated Both knockdown ferrostatin-1 treatment neutralized What’s more, transcriptionally regulated Specificity 1 (Sp1). overexpression enhanced it. Conclusion Upregulation activates Ascl4 transcription thus mediates ferroptosis. Hence, may a therapeutic target for intervention OA.

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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