Hyperglycemia modulates M1/M2 macrophage polarization via reactive oxygen species overproduction in ligature‐induced periodontitis

Journal of Periodontal Research, Journal Year: 2021, Volume and Issue: 56(5), P. 991 - 1005

Published: June 30, 2021

Abstract Background and objective Periodontitis in diabetic patients is characterized by enhanced inflammation aggravated tissue damage comparison with that non‐diabetic counterparts. The progression of periodontal under condition can be partly ascribed to hyperglycemia‐induced disturbance between immune activation resolution, where macrophages are capable participating given their plasticity response different stimuli. Herein, we aimed investigate the changes macrophage polarization periodontitis underlying mechanism. Materials Methods Type‐1 diabetes was induced injection streptozotocin (STZ, 60 mg/kg) Sprague‐Dawley rats. Rats N‐acetyl cysteine (NAC)‐treated groups received NAC dissolved drinking water (200 mg/kg/day). Experimental ligating 3–0 silk around left maxillary second molars for 4 weeks. Alveolar bone destruction tested micro‐computed tomography tartrate‐resistant acid phosphatase (TRAP) staining. M1/M2 detected immunohistochemistry RAW264.7 were cultured normal glucose (5.5 mM) or high environment (25 without (8 mmol/L). LPS (100 ng/ml) IL‐4 (20 used induce M1 M2 macrophages, respectively. qRT‐PCR, immunofluorescent staining, flow cytometry. Reactive oxygen species (ROS) accumulation fluorogenic probes. RANKL applied osteoclastogenic differentiation RAW264.7, osteoclast formation examined TRAP Results displayed infiltration lesions compared vehicle‐treated Under stimulation, culture elevated ROS level increased expression markers (iNOS, TNF‐α, IL‐6) whereas decreased (Arg‐1 CD206). Supernatants glucose‐treated glucose‐cultured cells. Decreasing via partially reversed effect on polarization. Meanwhile, daily intake rodent models inhibited polarization, which subsequently ameliorated alveolar loss numbers Conclusion These findings demonstrated hyperglycemia could polarize toward overproducing inflammatory condition, might take responsibility condition. Inhibiting restoring scavenger hopefully a potential adjunct treatment strategy periodontitis.

Language: Английский

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Osteoarthritis year in review 2020: biology

Osteoarthritis and Cartilage, Journal Year: 2020, Volume and Issue: 29(2), P. 143 - 150

Published: Nov. 24, 2020

This year in review about osteoarthritis biology highlights a selection of articles published between the 2019 and 2020 Osteoarthritis Research Society International (OARSI) World Congress meetings, within field biology. Highlights were selected from PubMed searches covering (OA) cartilage, subchondral bone, synovium aging. Subsequently, personal was based on new emerging themes together with common research topics that studied by multiple groups. Themes discussed include novel insights into inflammatory changes during OA, number noteworthy publications concerning role macrophages healthy osteoarthritic joints. Next, application mesenchymal stem cells as OA-dampening therapy is discussed, including possible ways to improve their efficacy pre-treatment. Other significant treatment OA metformin, enhancing autophagy alleviate involvement gastro-intestinal microbiome development symptoms structural damage are discussed. An effort made connect seemingly distant which overarching conclusion can be drawn over last promising breakthroughs have been achieved further understanding therapeutic possibilities explored.

Language: Английский

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Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7

Annals of the Rheumatic Diseases, Journal Year: 2022, Volume and Issue: 81(5), P. 676 - 686

Published: Jan. 20, 2022

To investigate the role of mechanical stress in cartilage ageing and identify mechanistic association during osteoarthritis (OA) progression.F-box WD repeat domain containing 7 (FBXW7) ubiquitin ligase expression chondrocyte senescence were examined vitro, experimental OA mice human cartilage. Mice with Fbxw7 knockout chondrocytes generated adenovirus-expressing (AAV-Fbxw7) was injected intra-articularly mice. Destabilised medial meniscus surgery performed to induce OA. Cartilage damage measured using Osteoarthritis Research Society International score changes determined. mRNA sequencing articular from control mice.Mechanical overloading accelerated cultured FBXW7 downregulated by primary cartilage, decreased patients OA, aged deletion induced catabolism mice, as manifested an upregulation p16INK4A, p21 Colx downregulation Col2a1 ACAN, which resulted exacerbation By contrast, intra-articular injection adenovirus expressing alleviated Mechanistically, transcription FBXW7-mediated MKK7 degradation, consequently stimulated JNK signalling. In particular, inhibition activity DTP3, a inhibitor, ameliorated degeneration CONCLUSIONS: is key factor between pathology

Language: Английский

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Osteoarthritis: New Insight on Its Pathophysiology

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(20), P. 6013 - 6013

Published: Oct. 12, 2022

Understanding of the basis osteoarthritis (OA) has seen some interesting advancements in recent years. It been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role this mechanism within pathogenesis and progression OA, as well formation ectopic osteophytes. Moreover, low-grade, chronic inflammation synovial lining gained central definition OA physiopathology, immunological mechanisms, innate but also adaptive, are now considered crucial driving tissue destruction. In addition, neuroinflammation sensitization mechanisms underlying causes pain chronicity characterized. This led to renewed which intended complex multifactorial joint pathology caused inflammatory metabolic factors damage. Since evidence can directly affect correct therapeutic approach an improved understanding these pathophysiological fundamental. To aim, review provides overview most updated on pathogenesis; it presents insights pathophysiology describing interplay between biochemical proposed drive destruction, mechanisms. although implications consequent beyond scope, suggestions for intervention have addressed.

Language: Английский

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Reprogramming Mitochondrial Metabolism in Synovial Macrophages of Early Osteoarthritis by a Camouflaged Meta‐Defensome

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(30)

Published: June 7, 2022

Osteoarthritis (OA) is a low-grade inflammatory and progressive joint disease, its progression closely associated with an imbalance in M1/M2 synovial macrophages. Repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype emerging as strategy to alleviate OA but compromised by unsatisfactory efficiency. In this study, reprogramming of mitochondrial dysfunction pioneered camouflaged meta-Defensome, which can transform high efficiency 82.3%. The meta-Defensome recognizes activated via receptor-ligand interactions accumulates mitochondria through electrostatic attractions. These meta-Defensomes are macrophage-membrane-coated polymeric nanoparticles decorated dual ligands co-loaded S-methylisothiourea MnO2 . Meta-Defensomes demonstrated successfully reprogram metabolism scavenging reactive oxygen species inhibiting NO synthase, thereby increasing transcription factor A expression restoring aerobic respiration. Furthermore, intravenously injected collagenase-induced osteoarthritis mice effectively suppress inflammation early OA, evident from Research Society International score. Therefore, serve novel practical approach repolarize promising therapeutic agent for impeding tclinic.

Language: Английский

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Novel plant-derived exosome-like nanovesicles from Catharanthus roseus: preparation, characterization, and immunostimulatory effect via TNF-α/NF-κB/PU.1 axis

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 20, 2023

Abstract Background Plant-derived exosomes-like nanovesicles (PDENs) have been found to be advantageous in disease treatment and drug delivery, but research on their biogenesis, compositional analysis, key marker proteins is still its infancy, which limits the standardized production of PDENs. Efficient preparation PDENs continues a major challenge. Results Novel PDENs-based chemotherapeutic immune modulators, Catharanthus roseus (L.) Don leaves-derived exosome-like (CLDENs) were isolated from apoplastic fluid. CLDENs membrane structured vesicles with particle size 75.51 ± 10.19 nm surface charge −21.8 mV. exhibited excellent stability, tolerating multiple enzymatic digestions, resisting extreme pH environments, remaining stable gastrointestinal simulating Biodistribution experiments showed that could internalized by cells, targeted at organs after intraperitoneal injection. The lipidomic analysis revealed CLDENs’ special lipid composition, contained 36.5% ether-phospholipids. Differential proteomics supported origin multivesicular bodies, six identified for first time. 60 ~ 240 μg/ml promoted polarization phagocytosis macrophages as well lymphocyte proliferation vitro. Administration 20 mg/kg alleviated white blood cell reduction bone marrow cycle arrest immunosuppressive mice induced cyclophosphamide. strongly stimulated secretion TNF-α, activated NF-κB signal pathway increased expression hematopoietic function-related transcription factor PU.1 both vitro vivo. To ensure steady supply CLDENs, plant culture systems C. established provide CLDENs-like had similar physical properties biological activities. Gram-level successfully obtained medium, yield was three times high original. Conclusions Our supports use nano-biomaterial stability biocompatibility, post-chemotherapy adjuvant therapy applications. Graphical

Language: Английский

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Electrospun fiber‐based immune engineering in regenerative medicine

Smart Medicine, Journal Year: 2024, Volume and Issue: 3(1)

Published: Feb. 1, 2024

Abstract Immune engineering, a burgeoning field within regenerative medicine, involves spectrum of strategies to optimize the intricate interplay between tissue biomaterials and host tissue. These are applied across different types various disease models, which encompasses finely modulating immune response at levels cells factors, aiming mitigate adverse effects like fibrosis persistent inflammation that may arise injury site consequently promote regeneration. With continuous progress in electrospinning technology, immunoregulatory capabilities electrospun fibers have gained substantial attention over years. Electrospun fibers, with their extracellular matrix‐like characteristics, high surface‐area‐to‐volume ratio, reliable pharmaceutical compound capacity, emerged as key players among engineering materials. This review specifically focuses on role fiber‐based emphasizing unique design strategies. Notably, actively engages by responses through four essential strategies: (i) surface modification, (ii) drug loading, (iii) physicochemical parameters, (iv) biological grafting. presents comprehensive overview mechanisms system injured tissues while unveiling adopted orchestrate regulation. Furthermore, explores current developmental trends limitations concerning function drive advancements its full potential.

Language: Английский

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Using Cu‐Based Metal–Organic Framework as a Comprehensive and Powerful Antioxidant Nanozyme for Efficient Osteoarthritis Treatment

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 26, 2024

Abstract Developing nanozymes with effective reactive oxygen species (ROS) scavenging ability is a promising approach for osteoarthritis (OA) treatment. Nonetheless, numerous lie in their relatively low antioxidant activity. In certain circumstances, some of these may even instigate ROS production to cause side effects. To address challenges, copper‐based metal–organic framework (Cu MOF) nanozyme designed and applied OA Cu MOF exhibits comprehensive powerful activities (i.e., SOD‐like, CAT‐like, •OH activities) while negligible pro‐oxidant (POD‐ OXD‐like activities). Collectively, more at various types than other Cu‐based antioxidants, such as commercial CuO single‐atom nanozyme. Density functional theory calculations also confirm the origin its outstanding enzyme‐like activities. vitro vivo results demonstrate that an excellent decrease intracellular levels relieve hypoxic microenvironment synovial macrophages. As result, can modulate polarization macrophages from pro‐inflammatory M1 anti‐inflammatory M2 subtype, inhibit degradation cartilage matrix efficient The biocompatibility protective properties make it valuable asset treating ROS‐related ailments beyond OA.

Language: Английский

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

Advanced Science, Journal Year: 2023, Volume and Issue: 11(9)

Published: Dec. 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.

Language: Английский

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Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 116, P. 109790 - 109790

Published: Feb. 1, 2023

Language: Английский

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