Reprogramming Macrophage Polarization, Depleting ROS by Astaxanthin and Thioketal‐Containing Polymers Delivering Rapamycin for Osteoarthritis Treatment

Advanced Science, Год журнала: 2023, Номер 11(9)

Опубликована: Дек. 14, 2023

Abstract Osteoarthritis (OA) is a chronic joint disease characterized by synovitis and cartilage destruction. The severity of OA highly associated with the imbalance between M1 M2 synovial macrophages. In this study, novel strategy designed to modulate macrophage polarization reducing intracellular reactive oxygen species (ROS) levels regulating mitochondrial function. A ROS‐responsive polymer synthesized self‐assemble astaxanthin autophagy activator rapamycin form nanoparticles (NP@Poly RHAPM ). vitro experiments show that NP@Poly significantly reduced ROS levels. Furthermore, restored membrane potential, increased glutathione (GSH) levels, promoted autophagy, hence successfully repolarizing macrophages into phenotype. This repolarization enhanced chondrocyte proliferation vitality while inhibiting apoptosis. vivo utilizing an anterior cruciate ligament transection (ACLT)‐induced mouse model revealed anti‐inflammatory cartilage‐protective effects , effectively mitigating progression. Consequently, findings suggest intra‐articular delivery nanocarrier systems holds significant promise as potential effective therapeutic for treatment.

Язык: Английский

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Hydrogels for ameliorating osteoarthritis: Mechanical modulation, anti‐inflammation, and regeneration

BMEMat, Год журнала: 2024, Номер 2(2)

Опубликована: Март 1, 2024

Abstract Osteoarthritis (OA) is a chronic and degenerative disease with limited clinical options for effective suppression. Recently, significant endeavors have been explored to reveal its pathogenesis develop treatments against OA. Hydrogels, designed striking resemblance the extracellular matrix, offer biomimetic interaction biological tissues, presenting promising avenue OA amelioration. As result, biocompatible hydrogels erected incorporating on‐demand bioactivities optimize intra‐articular microenvironment, thereby alleviating symptoms fostering eventual regeneration of articular joints. This review highlights collaborative objectives underlying establishment this tissue encompassing mechanical modulation, anti‐inflammation, regeneration. Specifically, we consolidate recent advances in hydrogel‐based biomaterials, serving as engineering scaffolds replicate lubrication properties natural joints or bioactive agent‐loaded vehicles combat localized inflammation. Additionally, function cell facilitate maintenance cellular homeostasis contribute advancement cartilage Finally, outlines prospective directions hydrogel‐mediated therapies.

Язык: Английский

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Exosomes loaded a smart bilayer-hydrogel scaffold with ROS-scavenging and macrophage-reprogramming properties for repairing cartilage defect

Bioactive Materials, Год журнала: 2024, Номер 38, С. 137 - 153

Опубликована: Апрель 27, 2024

Язык: Английский

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Skatole Alleviates Osteoarthritis by Reprogramming Macrophage Polarization and Protecting Chondrocytes

Research, Год журнала: 2025, Номер 8

Опубликована: Янв. 1, 2025

Osteoarthritis (OA) is the most prevalent joint disease, yet effective disease-modifying OA drugs (DMOADs) remain elusive. Targeting macrophage polarization has emerged as a promising avenue for treatment. This study identified skatole through high-throughput screening an efficient modulator of polarization. In vivo experiments demonstrated that administration markedly reduced synovitis and cartilage damage in both destabilization medial meniscus (DMM)-induced mice monosodium iodoacetate (MIA)-induced rats. Mechanistically, activated signal transducer activator transcription 6 (Stat6) signaling, promoting M2 polarization, while inhibiting nuclear factor-κB (NFκB) mitogen-activated protein kinase (MAPK) signaling pathways to suppress M1 RNA-sequencing analysis, targeted metabolomics, mitochondrial stress tests further revealed treatment shifted macrophages toward oxidative phosphorylation energy production. Additionally, it up-regulated genes associated with glutathione metabolism reactive oxygen species (ROS) pathways, reducing intracellular ROS The CUT&Tag assay results indicated downstream factor p65 NFκB can directly bind gene loci related inflammation, phosphorylation, metabolism, thereby modulating expression. regulatory process inhibited by skatole. At chondrocyte level, conditional medium from skatole-treated balanced anabolism catabolism mouse chondrocytes apoptosis. IL1β-treated chondrocytes, suppressed inflammation without affecting apoptosis or anabolism. Overall, maintains immune microenvironment homeostasis joints preserves function balancing catabolism, effectively alleviating OA. These findings suggest skatole’s potential DMOAD.

Язык: Английский

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A Baicalin‐Based Functional Polymer in Dynamic Reversible Networks Alleviates Osteoarthritis by Cellular Interactions

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Osteoarthritis (OA) is increasingly recognized as a whole‐organ disease predominantly affecting the elderly, characterized by typical alterations in subchondral bone and cartilage, along with recurrent synovial inflammation. Despite availability of various therapeutics medications, complete resolution OA remains elusive. In this study, novel functional hydrogels are developed integrating natural bioactive molecules for treatment. Specifically, baicalin (Bai) combined 2‐hydroxyethyl acrylate (HEA) to form polymerizable monomer (HEA‐Bai) through esterification, which subjected reversible addition‐fragmentation chain transfer (RAFT) polymerization produce Bai‐based polymer (P m ). These macromolecules incorporated into Schiff‐base hydrogels, demonstrate excellent mechanical properties self‐healing performance. Notably, formulations taken up fibroblast‐like synoviocytes (FLSs), where they regulate glycolysis. Mechanistically, inhibition yes‐associated protein 1 (YAP1) suppressed FLSs glycolysis reduced secretion inflammatory factors, including interleukin 1β (IL‐1β), IL‐6, IL‐8. Furthermore, hydrogel (AG‐P )‐OC, severing lubricant nutrient, prolonged joint retention Bai, thereby reducing cartilage degradation Meanwhile, )‐OC alleviated pain targeting YAP1 signaling inhibiting macrophage recruitment polarization. Taken together, flavonoid‐based injectable exhibits enhanced biocompatibility efficacy against OA.

Язык: Английский

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Remodeling the Proinflammatory Microenvironment in Osteoarthritis through Interleukin-1 Beta Tailored Exosome Cargo for Inflammatory Regulation and Cartilage Regeneration

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Osteoarthritis (OA) presents a significant therapeutic challenge, with few options for preserving joint cartilage and repairing associated tissue damage. Inflammation is pivotal factor in OA-induced deterioration synovial inflammation. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (HucMSCs) have gained recognition as promising noncellular modality, but their use hindered by the challenge of harvesting sufficient number effective efficacy. Given that HucMSCs are highly sensitive to microenvironmental signals, we hypothesized priming within proinflammatory environment would increase secreted enhanced anti-inflammatory properties. Subsequent miRNA profiling pathway analysis confirmed interleukin-1 beta (IL-1β)-induced (C-Exos) exert positive effects through regulation signaling modulation. In vitro experiments revealed C-Exos enhance chondrocyte functionality matrix production, well macrophage polarization, thereby enhancing repair. were encapsulated hyaluronic acid hydrogel microspheres (HMs) ensure sustained release, leading substantial improvements inflammatory microenvironment regeneration rat OA model. This study outlines strategy tailor exosome cargo regenerative purposes, functionalized HMs demonstrating potential treatment.

Язык: Английский

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Ultrasmall Prussian Blue Nanozyme Attenuates Osteoarthritis by Scavenging Reactive Oxygen Species and Regulating Macrophage Phenotype

Nano Letters, Год журнала: 2024, Номер 24(37), С. 11697 - 11705

Опубликована: Сен. 3, 2024

Osteoarthritis (OA) is a degenerative joint disease characterized by obscure etiology and unsatisfactory therapeutic outcomes, making the development of new efficient therapies urgent. Superfluous reactive oxygen species (ROS) have historically been considered one crucial factors inducing pathological progression OA. Ultrasmall Prussian blue nanoparticles (USPBNPs), approximately sub-5 nm in size, are developed regulating configuration polyvinylpyrrolidone chains. USPBNPs display an excellent ROS eliminating capacity catalase-like activity, capable decomposing hydrogen peroxide (H

Язык: Английский

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Nano-enzyme hydrogels for cartilage repair effectiveness based on ternary strategy therapy

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(25), С. 6242 - 6256

Опубликована: Янв. 1, 2024

An artificial nano-enzyme-enhanced hydrogel was developed to treat OA through a ternary synergistic strategy of efficiently driving O 2 production from endogenous ROS in chondrocytes and maintaining lubrication at the articular cartilage interface.

Язык: Английский

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PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Июль 17, 2024

Abstract Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals chondrocyte biology, but their roles the associated mechanisms in stress-associated senescence OA not elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of proteins, which belongs to Na + /H Exchanger (NHE) regulatory factor family, is key biomechanically induced mitochondrial dysfunction during progression. PDZK1 reduced by overload, diminished articular cartilage patients, aged mice mice. Pdzk1 knockout chondrocytes exacerbates overload-induced degeneration, whereas intraarticular injection adeno-associated virus-expressing had therapeutic effect. Moreover, loss impaired function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content increased reactive oxygen species (ROS) production. supplementation or mitoubiquinone (MitoQ) application alleviated degeneration significantly protected functions. MRNA sequencing from controls showed deficiency interfered through inhibiting Hmgcs2 increasing its ubiquitination. Our results suggested plays crucial role mediating excessive load-induced dysfunction. overexpression preservation functions MitoQ might present new approach OA.

Язык: Английский

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Research progress on macrophage polarization during osteoarthritis disease progression: a review

Journal of Orthopaedic Surgery and Research, Год журнала: 2024, Номер 19(1)

Опубликована: Сен. 28, 2024

Язык: Английский

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