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

Orthopaedic Surgery, Journal Year: 2024, Volume and Issue: 16(3), P. 532 - 550

Published: Jan. 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

Language: Английский

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4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: April 24, 2023

Abstract Background Septic acute kidney injury (S-AKI) is the leading form of failure among hospitalized patients, and inflammatory response involved in this process. 4-octyl itaconate (4-OI) a multi-target derivative with potent anti-inflammatory action. However, it remains elusive whether how 4-OI contributes to regulation S-AKI. Methods We employed lipopolysaccharide (LPS)-induced AKI murine model explored potential renoprotective effect vivo . In vitro experiments, BUMPT cells, renal tubular cell line, were conducted examine effects on inflammation, oxidative stress, mitophagy. Moreover, STAT3 plasmid was transfected cells investigate role signaling 4-OI-administrated state. Results demonstrate that protects against S-AKI through suppressing inflammation stress enhancing significantly reduced levels Scr, BUN, Ngal as well LPS-induced mice. restrained by reducing macrophage infiltration expression IL-1β NLRP3 septic kidney. also ROS levels, cleaved caspase-3 boosted antioxidants such HO-1, NQO1 addition, treatment promoted Mechanistically, activated Nrf2 suppressed phosphorylated vitro. Molecular docking revealed binding affinity towards STAT3. ML385, specific inhibitor, partially repressed anti-oxidative restricted mitophagy induced Transfected provoked Conclusion These data suggest ameliorates overactivation pathway, inactivation Our study identifies promising pharmacologic for

Language: Английский

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Osteoarthritis: Role of Peroxisome Proliferator-Activated Receptors

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13137 - 13137

Published: Aug. 24, 2023

Osteoarthritis (OA) represents the foremost degenerative joint disease observed in a clinical context. The escalating issue of population aging significantly exacerbates prevalence OA, thereby imposing an immense annual economic burden on societies worldwide. current therapeutic landscape falls short offering reliable pharmaceutical interventions and efficient treatment methodologies to tackle this growing problem. However, scientific community continues dedicate significant efforts towards advancing OA research. Contemporary studies have discovered that progression may be slowed through strategic influence peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated within nuclear hormone receptor family. three distinctive subtypes-PPARα, PPARβ/δ, PPARγ-find expression across broad range cellular terminals, thus managing multitude intracellular metabolic operations. activation PPARγ PPARα has been shown efficaciously modulate NF-κB signaling pathway, AP-1, other oxidative stress-responsive conduits, leading inhibition inflammatory responses. Furthermore, confer protection chondrocytes by exerting control over its autophagic behavior. In summation, both emerged as promising potential targets for development effective treatments.

Language: Английский

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Injectable hydrogel loaded with 4-octyl itaconate enhances cartilage regeneration by regulating macrophage polarization

Biomaterials Science, Journal Year: 2023, Volume and Issue: 11(7), P. 2445 - 2460

Published: Jan. 1, 2023

Macrophages play a distinctive role in the early stage of inflammation after cartilage defects. Previous studies have shown that macrophages can express different phenotypes, among which M2 polarization is important to maintain balance inflammatory microenvironment and promote regeneration. In this study, 4-octyl itaconic acid (4-OI), derivative endogenous metabolite acid, was used regulate behavior enhance repair. Oxidized sodium alginate (OSA) gelatin (GEL) were selected as materials form injectable hydrogels with function sustained release 4-OI. vivo vitro experiments verified OSA/GEL hydrogel system loaded 4-OI could macrophage inhibit reaction. A rat knee joint defect model further confirmed its promoting regeneration later stage. successfully fabricated vehicle for delivering 4-OI, evidently alleviate reaction thus accelerate tissue The results study provide new method subsequent by regulating immune response.

Language: Английский

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Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways

iScience, Journal Year: 2023, Volume and Issue: 26(2), P. 105936 - 105936

Published: Jan. 5, 2023

Osteoarthritis (OA) is a trauma-/age-related degenerative disease characterized by chronic inflammation as one of its pathogenic mechanisms. Mulberroside A (MA), natural bioactive withanolide, demonstrates anti-inflammatory properties in various diseases; however, little known about the effect MA on OA. We aim to examine role OA and identify potential mechanisms through which it protects articular cartilage. In vitro, improved inflammatory response, anabolism, catabolism IL-1β-induced chondrocytes. The chondroprotective effects were attributed suppressing MAPK, NF-κB, PI3K-AKT-mTOR signaling pathways, well promoting autophagy process. vivo, intra-articular injection reduced cartilage destruction reversed change anabolic catabolic-related proteins destabilized medial meniscus (DMM)-induced models. Thus, study indicates that exhibits might be promising agent for treatment.

Language: Английский

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Thrombospondin-1-mediated crosstalk between autophagy and oxidative stress orchestrates repair of blast lung injury

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(3), P. 167026 - 167026

Published: Jan. 17, 2024

Language: Английский

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Unraveling the path to osteoarthritis management: targeting chondrocyte apoptosis for therapeutic intervention

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: May 17, 2024

Osteoarthritis (OA) is a chronic disease affecting joints and further causing disabilities. This affects around 240 million people worldwide. It multifactorial disease, its etiology difficult to determine. Although numerous therapeutic strategies are available, the therapies aimed at reducing pain improving patients’ quality of life. Hence, there an urgent need develop disease-modifying drugs (DMOAD) that can reverse or halt OA progression. Apoptosis cell removal process important in maintaining homeostatic mechanisms development sustaining population. The apoptosis chondrocytes believed play role progression due poor self-repair abilities maintain extracellular matrix (ECM). targeting chondrocyte be one potential management. There various mediators targets available inhibit such as autophagy, endoplasmic reticulum (ER) stress, oxidative inflammation. As such, this review highlights importance reduce apoptosis.

Language: Английский

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Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway

European journal of medical research, Journal Year: 2022, Volume and Issue: 27(1)

Published: Oct. 17, 2022

Abstract Objectives This study aims to investigate the effects of Icariin (ICA) on interleukin-1β (IL-1β)-induced osteoarthritis (OA) and its potential mechanism action. Methods SW1353 chondrocytes were pretreated with ICA for 2 h, followed by stimulation IL-1β mimic OA. Expression levels matrix metalloproteinases (MMP-3) collagen II determined using real-time PCR Western blot assays. Autophagy activation (by ICA) or inhibition shRNA) was based expression ULK1, Beclin-1, LC3-II/I, p62, analysis. The phosphorylation PI3K, Akt, mTOR, ULK1 also detected Results increased MMP-3 overproduction, induced degradation, reduced level autophagy-associated proteins, including LC3-II/I. In contrast, pretreatment attenuated IL-1β-induced expression, autophagy-related proteins. decreased mTOR phosphorylation, production autophagy. Short hairpin RNA-mediated knockdown led PI3K/Akt/mTOR pathway, which reversed protective ICA. Conclusions Our findings indicate that can induce autophagy regulating PI3K/AKT/mTOR/ULK1 signaling pathway. suggests may be effective treating

Language: Английский

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Dimethyl itaconate is effective in host-directed antimicrobial responses against mycobacterial infections through multifaceted innate immune pathways

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 8, 2023

Itaconate, a crucial immunometabolite, plays critical role in linking immune and metabolic functions to influence host defense inflammation. Due its polar structure, the esterified cell-permeable derivatives of itaconate are being developed provide therapeutic opportunities infectious inflammatory diseases. Yet, it remains largely uncharacterized whether have potentials promoting host-directed therapeutics (HDT) against mycobacterial infections. Here, we report dimethyl (DMI) as promising candidate for HDT both Mycobacterium tuberculosis (Mtb) nontuberculous mycobacteria by orchestrating multiple innate programs.DMI per se has low bactericidal activity Mtb, M. bovis Bacillus Calmette-Guérin (BCG), avium (Mav). However, DMI robustly activated intracellular elimination strains (Mtb, BCG, Mav, even multidrug-resistant Mtb) macrophages vivo. significantly suppressed production interleukin-6 -10, whereas enhanced autophagy phagosomal maturation, during Mtb infection. DMI-mediated partly contributed antimicrobial defenses macrophages. Moreover, downregulated activation signal transducer activator transcription 3 signaling infection with Mav.Together, potent anti-mycobacterial activities vivo through multifaceted ways defenses. may bring light new mycobacteria, which infections often intractable antibiotic resistance.

Language: Английский

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Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7411 - 7411

Published: July 5, 2024

Advancing age is associated with several age-related diseases (ARDs), musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic contributing towards considerable number patients, a deeper understanding bone aging the need hour. One underlying factors cellular senescence and its secretory phenotype (SASP). SASP comprises pro-inflammatory markers, cytokines chemokines that arrest cell growth development. The accumulation over years leads to chronic low-grade inflammation advancing age, also known as inflammaging. pathways molecular mechanisms focused on inflammaging are currently limited but increasingly being explored. Most genes, involved in coincide those cancer other ARDs like osteoarthritis (OA). Thus, exploring these using techniques sequencing, identifying combatting them most suitable approach crucial for healthy early detection ARDs. Several approaches can be used aid regeneration reduce bone. These may pharmacological, non-pharmacological lifestyle interventions. increasing evidence intricate relationship between aging, senescence, ARDs, anti-aging strategies marrow (BM).

Language: Английский

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