Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies

Orthopaedic Surgery, Год журнала: 2024, Номер 16(3), С. 532 - 550

Опубликована: Янв. 31, 2024

Osteoarthritis (OA) is the most common chronic degenerative joint disease in middle‐aged and elderly people, characterized by pain dysfunction. Macrophages are key players OA pathology, their activation state has been studied extensively. Various studies have suggested that macrophages might respond to stimuli microenvironment changing phenotypes pro‐inflammatory or anti‐inflammatory phenotypes, which called macrophage polarization. accumulate become polarized (M1 M2) many tissues, such as synovium, adipose tissue, bone marrow, mesenchymal tissues joints, while resident well other stromal cells, including fibroblasts, chondrocytes, osteoblasts, form function an integrated unit. In this study, we focus exclusively on synovial macrophages, tissue osteoclasts, investigate roles development of OA. We review recent findings related polarization OA, pathogenesis, molecular pathways, therapeutics. summarize several signaling pathways reprogramming NF‐κB, MAPK, TGF‐β, JAK/STAT, PI3K/Akt/mTOR, NLRP3. Of note, despite increasing availability treatments for osteoarthritis, like intra‐articular injections, surgery, cellular therapy, demand more effective clinical therapies remained steady. Therefore, also describe current prospective therapeutic methods deem be a target, physical stimulus, chemical compounds, biological molecules, enhance cartilage repair alleviate progression

Язык: Английский

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Opsonization Inveigles Macrophages Engulfing Carrier‐Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy

Advanced Science, Год журнала: 2024, Номер 11(22)

Опубликована: Апрель 9, 2024

Abstract Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease‐modifying treatments for OA are currently lacking. Because inflammation mediated an imbalance of M1/M2 macrophages in the synovial cavities contributes to progression, regulating M1 M2 polarization can be potential therapeutic strategy. Basing on inherent immune mechanism pathological environment OA, immunoglobulin G‐conjugated bilirubin/JPH203 self‐assembled nanoparticle (IgG/BRJ) developed, its evaluated. After intra‐articular administration, IgG conjugation facilitates recognition engulfment nanoparticles macrophages. The internalized disassemble response increased oxidative stress, released bilirubin (BR) JPH203 scavenge reactive oxygen species (ROS), inhibit nuclear factor kappa‐B pathway, suppress activated mammalian target rapamycin result repolarization enhance M2/M1 ratios. Suppression IgG/BRJ promotes protection repair rat model, thereby improving outcomes. This strategy opsonization involving engulf carrier‐free BR/JPH203 therapy holds great intervention treatment.

Язык: Английский

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Inflammation-Responsive Nanoagents for Activatable Photoacoustic Molecular Imaging and Tandem Therapies in Rheumatoid Arthritis

ACS Nano, Год журнала: 2024, Номер 18(3), С. 2231 - 2249

Опубликована: Янв. 8, 2024

Rheumatoid arthritis (RA) severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, representing a pressing public health concern. The pathogenesis of RA includes excessive production proinflammatory cytokines harmful oxygen-derived free radicals, such as nitric oxide (NO), which constitute vital targets for precise diagnosis effective treatment RA. In this study, we introduce an advanced nanoagent that integrates microenvironment-activatable photoacoustic (PA) imaging with multitarget synergistic A highly sensitive organic probe NO-tunable energy transformation molecular geometry is developed, enables strong near-infrared absorption turn-on PA signal, active intramolecular motion could further boost conversion. coassembled inflammation-responsive prodrug to construct theranostic nanoagent, on macrophage-derived cell membrane natural tropism inflammatory sites camouflaged improve targeting ability inflamed joints. not only sensitively detect differentiate severity but also efficiently alleviate symptoms function. combination activatable probe-mediated NO scavenging on-demand activation anti-inflammatory significantly inhibits factors promotes macrophage repolarization from M1 M2 phenotype. This meticulously designed ingeniously RA-specific therapy, rendering tremendous promise intervention RA-related diseases.

Язык: Английский

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Sequential Targeting Chondroitin Sulfate‐Bilirubin Nanomedicine Attenuates Osteoarthritis via Reprogramming Lipid Metabolism in M1 Macrophages

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Abstract The infiltration and excessive polarization of M1 macrophages contribute to the induction persistence low‐grade inflammation in joint‐related degenerative diseases such as osteoarthritis (OA). lipid metabolism dysregulation promotes macrophage by coordinating compensatory pathways inflammatory oxidative stress responses. Here, a self‐assembling, licofelone‐loaded nanoparticle (termed LCF‐CSBN), comprising chondroitin sulfate bilirubin joined an ethylenediamine linker, is developed selectively reprogram activation. LCF‐CSBN internalized via CD44‐mediated endocytosis targets Golgi apparatus accompanied with reactive oxygen species‐responsive release licofelone (LCF, dual inhibitor arachidonic acid metabolism). effectively M2 transition reprogramming apparatus‐related sphingolipid metabolism. Intra‐articularly injected retains joint for up 28 days accumulates into macrophages. Moreover, can attenuate inflammation, stress, cartilage degeneration OA model rats. These findings indicate promising potential lipid‐metabolism‐reprogramming targeted therapy OA.

Язык: Английский

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Metabolic reprogramming of macrophages by a nano-sized opsonization strategy to restore M1/M2 balance for osteoarthritis therapy

Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 469 - 489

Опубликована: Фев. 11, 2025

Язык: Английский

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Osteoarthritis year in review 2023: Biology

Osteoarthritis and Cartilage, Год журнала: 2023, Номер 32(2), С. 148 - 158

Опубликована: Ноя. 7, 2023

Great progress continues to be made in our understanding of the multiple facets osteoarthritis (OA) biology. Here, we review major advances this field and towards therapy development over past year, highlighting a selection relevant published literature from PubMed search covering year end April 2022 2023. The selected articles have been arranged themes. These include 1) molecular regulation articular cartilage implications for OA, 2) mechanisms subchondral bone remodelling, 3) role synovium inflammation, 4) age-related changes including matrix stiffening, cellular senescence, mitochondrial dysfunction, metabolic impaired autophagy, 5) peripheral OA pain. Progress responsible aspects biology is unravelling novel therapeutic targets disease modification.

Язык: Английский

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Histone demethylases in the regulation of immunity and inflammation

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Июнь 23, 2023

Abstract Pathogens or danger signals trigger the immune response. Moderate response activation removes pathogens and avoids excessive inflammation tissue damage. Histone demethylases (KDMs) regulate gene expression play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal of KDMs is closely associated with pathogenesis various inflammatory diseases such as liver fibrosis, lung injury, autoimmune diseases. Despite becoming exciting targets for diagnosing treating these diseases, role enzymes regulation still unclear. Here, we review underlying mechanisms through which immune-related pathways responses. In addition, also discuss future applications inhibitors

Язык: Английский

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Targeting YAP1‐regulated Glycolysis in Fibroblast‐Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression

Advanced Science, Год журнала: 2023, Номер 11(5)

Опубликована: Дек. 3, 2023

Abstract The interplay between immune cells/macrophages and fibroblast‐like synoviocytes (FLSs) plays a pivotal role in initiating synovitis; however, their involvement metabolic disorders, including diabetic osteoarthritis (DOA), is largely unknown. In this study, single‐cell RNA sequencing (scRNA‐seq) employed to investigate the synovial cell composition of DOA. A significant enrichment activated macrophages within eight distinct clusters found DOA synovium. Moreover, it demonstrated that increased glycolysis FLSs key driver for patients’ macrophage infiltration polarization. addition, yes‐associated protein 1 (YAP1)/thioredoxin‐interacting (TXNIP) signaling axis play crucial regulating glucose transporter (GLUT1)‐dependent FLSs, thereby controlling expression series adhesion molecules such as intercellular molecule‐1 (ICAM‐1) which may subsequently fine‐tune M1‐polarized patients db/db OA mice. For treatment, M1 membrane‐camouflaged Verteporfin (Vt)‐loaded PLGA nanoparticles (MVPs) are developed ameliorate progression by YAP1/TXNIP axis, thus suppressing macrophages. results provide several novel insights into pathogenesis offer promising treatment approach

Язык: Английский

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The role and intervention of mitochondrial metabolism in osteoarthritis

Molecular and Cellular Biochemistry, Год журнала: 2023, Номер 479(6), С. 1513 - 1524

Опубликована: Июль 24, 2023

Abstract Osteoarthritis (OA), a prevalent degenerative joint disease, affects substantial global population. Despite the elusive etiology of OA, recent investigations have implicated mitochondrial dysfunction as significant factor in disease pathogenesis. Mitochondria, pivotal cellular organelles accountable for energy production, exert essential roles metabolism. Hence, can broad-ranging effects on various processes OA development. This comprehensive review aims to provide an overview metabolic alterations occurring and elucidate diverse mechanisms through which contribute These encompass heightened oxidative stress inflammation, perturbed chondrocyte metabolism, compromised autophagy. Furthermore, this will explore potential interventions targeting metabolism means impede or decelerate progression OA. In summary, offers understanding involvement underscores prospective intervention strategies.

Язык: Английский

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Microenvironment‐Activatable Probe for Precise NIR‐II Monitoring and Synergistic Immunotherapy in Rheumatoid Arthritis

Advanced Materials, Год журнала: 2024, Номер 36(48)

Опубликована: Окт. 6, 2024

Rheumatoid arthritis (RA) represents an insidious autoimmune inflammatory disorder that severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, posing a serious public health problem. Here, advanced theranostic probe is introduced integrates activatable second near-infrared (NIR-II) fluorescence imaging for precise RA diagnosis with multi-pronged treatments. A novel molecular comprising long-wavelength aggregation-induced emission unit manganese carbonyl cage motif synthesized, which enables NIR-II activation concurrently releasing therapeutic carbon monoxide (CO) gas in inflamed microenvironment. This self-assembles into biocompatible nanoprobe, subsequently conjugated anti-IL-6R antibody to afford active-targeting ability of RA. The nanoprobe exhibits significant turn-on signal at lesion, enabling highly sensitive real-time monitoring. combination ROS scavenging, on-demand CO release, IL-6 signaling blockade results potent effect synergistic immunomodulation impact, significantly alleviating symptoms preventing destruction. research introduces paradigm development high-performance, strategies facilitate detection enhanced treatment RA-related diseases.

Язык: Английский

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