Application and progress of smart hydrogel microspheres for regulating oxidative stress in osteoarthritis

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160620 - 160620

Published: Feb. 1, 2025

Language: Английский

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Neutralization of acyl CoA binding protein (ACBP) for the experimental treatment of osteoarthritis

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract The plasma concentrations of acyl CoA binding protein (ACBP) encoded by the gene diazepam inhibitor ( DBI ) are increased in patients with severe osteoarthritis (OA). Here, we show that knee OA induces a surge ACBP/DBI mice subjected to surgical destabilization one hind limb. Knockout Dbi or intraperitoneal (i.p.) injection monoclonal antibody (mAb) neutralizing attenuates progression this model, supporting pathogenic role for OA. Furthermore, anti-ACBP/DBI mAb was also effective against after its intraarticular (i.a.) injection, as monitored sonography, revealing capacity locally reduce inflammation over time. In addition, i.a. improved functional outcomes, indicated reduced weight imbalance caused At anatomopathological level, mitigated histological signs joint destruction and synovial inflammation. Of note, blunted OA-induced ACBP/DBI, well other inflammatory factors including interleukin-1α, interleukin-33, tumor necrosis factor. These findings potentially translatable because joints from express both receptor GABA A Rγ2. Moreover, novel recognizing an epitope conserved between human mouse demonstrated similar efficacy mitigating anti-mouse ACBP/DBI-only mAb. conclusion, might constitute promising therapeutic target treatment

Language: Английский

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Kojic acid alleviates osteoarthritis by attenuating inflammation and restoring impaired autophagy through regulating NF-κB and PI3K/AKT/mTOR signaling pathways: An in vivo and in vitro study

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 114022 - 114022

Published: Jan. 6, 2025

Osteoarthritis (OA) is the most prevalent joint disorder globally, causing a substantial and increasing socioeconomic burden. Kojic acid (KA) presented potential biological roles in regulating inflammation autophagy, which was implicated OA progression. However, its role chondrocytes has not been reported. To do so, this study aims to explore chondroprotective effect of KA elucidate regulatory mechanisms. IL-1β vitro used induce OA-like phenotypes. Cell viability measured by cell counting kit-8 assay. RT-qPCR, western blotting, as well immunofluorescence staining were assess protein RNA expression inflammatory (COX2 iNOS), catabolic (MMP13 MMP3), anabolic (collagen II, aggrecan SOX9), signaling pathways factors. Destabilized medial meniscus (DMM) surgery adopted build model vivo. After consecutive 8 weeks intra-articular injection KA, X-ray, μ-CT, histological staining, immunohistochemistry evaluate effects on articular cartilage did affect chondrocyte viability. notably elevated factors expression, simultaneously, inhibited vitro. Mechanistically, significantly suppressed activated NF-κB PI3K/AKT/mTOR pathways. Moreover, impaired autophagy restored KA. Inhibition 3-MA diminished Intra-articular can alleviate DMM-induced damage Collectively, our work first demonstrate that osteoarthritis attenuatinginflammationand restoring through relevant This vivo provides strong evidence supportingKA novel valuable approach for treating OA.

Language: Английский

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Mendelian randomization analysis to identify potential drug targets for osteoarthritis

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0316824 - e0316824

Published: Feb. 11, 2025

Background Osteoarthritis (OA) is a prevalent chronic joint disease for which there lack of effective treatments. In this study, we used Mendelian randomization analysis to identify circulating proteins that are causally associated with OA-related traits, providing important insights into potential drug targets OA. Method Causal associations between 1553 and five traits were assessed in large-scale two-sample MR analyses using Wald ratio or inverse variance weighting, the results corrected Bonferroni. addition, sensitivity performed validate reliability results, including reverse Steiger filtering ensure causal direction OA; Bayesian co-localization phenotypic scanning eliminate confounding effects horizontal pleiotropy. External validation was exclude incidental findings novel plasma protein quantitative trait loci. Finally, online tool Enrichr utilized screen drugs molecular docking predict binding modes energies most stable likely drugs. Result Four ultimately found be reliably three features: DNAJB12 USP8 knee OA, IL12B spinal RGMB thumb The ORs above 1.51 (95% CI, 1.26–1.81), 1.72 1.42–2.08), 0.87 0.81–0.92), 0.59 0.47–0.75), respectively. Drug-predicting small molecules (doxazosin, XEN 103, montelukast) simultaneously target proteins, DNAJB12, USP8, IL12B, docked well. Conclusion Based on our comprehensive analysis, can draw conclusion relationship genetic levels , risk respective OA.They may options OA screening prevention clinical practice. They also serve as candidate future mechanism exploration selection.

Language: Английский

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Aberrant anabolism hinders constructive metabolism of chondrocytes by pharmacotherapy in osteoarthritis

Bone and Joint Research, Journal Year: 2025, Volume and Issue: 14(3), P. 199 - 207

Published: March 5, 2025

Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss alteration of other joint structures result from complex interaction multiple risk factors, mechanical overload consistently playing central role. This generates inflammatory response in the due to activation innate immune chondrocytes, which occurs through various cellular mechanisms. Moreover, factors associated obesity, being overweight, metabolic syndrome enhance both locally systemically. OA only cells present articular cartilage, are therefore inflamed initiate anabolic process attempt repair damaged tissue, ultimately results aberrant dysfunctional process. Under these circumstances, where continues be subjected chronic stress, proposing treatment that stimulates chondrocytes' restore tissue structure does not appear target high likelihood success. In fact, drugs proposed for have yet demonstrate efficacy. By contrast, strategies focused on pharmacologically managing component, at systemic levels, shown promise. Therefore, prioritizing control pro-inflammatory pathways presents most viable promising strategy effective management OA. As research continues, this approach may offer best opportunity alleviate burden incapacitating disease.

Language: Английский

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Research progress and prospect of MAPK signaling pathway in knee osteoarthritis

European Journal of Orthopaedic Surgery & Traumatology, Journal Year: 2025, Volume and Issue: 35(1)

Published: March 26, 2025

The knee joint, one of the most vulnerable joints in human body, is susceptible to degenerative changes due factors such as aging, obesity, trauma, inflammation, and genetic predisposition. These contribute primary or secondary degeneration joint cartilage bone hyperplasia. Knee osteoarthritis (KOA), a prevalent condition particularly among elderly, significantly impacts patients' quality life. Aberrant activation cellular signaling pathways, namely NF-κB, MAPK, Wnt has been identified key factor pathogenesis KOA. pathways degradation, disruption anabolic-catabolic balance within articular cartilage. Understanding precise roles these crucial for developing targeted therapies prevent treat OA. Therefore, further exploration essential develop more effective therapeutic strategies.

Language: Английский

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