Therapeutic potential in rheumatic diseases of extracellular vesicles derived from mesenchymal stromal cells

Nature Reviews Rheumatology, Journal Year: 2023, Volume and Issue: 19(11), P. 682 - 694

Published: Sept. 4, 2023

Language: Английский

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Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment

ACS Nano, Journal Year: 2024, Volume and Issue: 18(11), P. 8125 - 8142

Published: March 7, 2024

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of the articular cartilage and inflammation. Mesenchymal stem cells' (MSCs) transplantation in OA treatment emerging, but its clinical application still limited low efficiency oriented differentiation. In our study, to improve therapeutic efficiencies MSCs carbonic anhydrase IX (CA9) siRNA (siCA9)-based inflammation regulation Kartogenin (KGN)-based chondrogenic differentiation, combination strategy nanomedicine codelivering KGN siCA9 (AHK-CaP/siCA9 NPs) was used. vitro results demonstrated that these NPs could inflammatory microenvironment through repolarization M1 macrophages M2 phenotype downregulating expression levels CA9 mRNA. Meanwhile, also enhance chondrogenesis bone marrow-derived mesenchymal cells (BMSCs) upregulating pro-chondrogenic TGF-β1, ACAN, Col2α1 mRNA levels. Moreover, an advanced mouse model, compared with BMSCs alone group, lower synovitis score OARSI were found group plus AHK-CaP/siCA9 NPs, suggesting this approach effectively inhibit promote regeneration progression. Therefore, synchronization regulating macrophage reprogramming (CA9 gene silencing) promoting differentiation agent (KGN) may be potential maximize for treatment.

Language: Английский

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Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 20, 2024

Abstract Background and aims Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of cartilage, synovial inflammation, subchondral bone hyperplasia. The tissue plays pivotal role in cartilage regulation. Exosomes (EXOs), small membrane-bound vesicles released cells into extracellular space, are crucial mediating intercellular communication facilitating exchange information between tissues. Our study aimed to devise hydrogel microsphere infused with SOD3-enriched exosomes (S-EXOs) protect introduce novel, effective approach for OA treatment. Materials methods We analyzed single-cell sequencing data from 4247 obtained GEO database. Techniques such as PCR, Western Blot, immunofluorescence (IF), assays measure oxidative stress levels were employed validate cartilage-protective properties identified key protein, SOD3. In vivo, mice received intra-articular injections S-EXOs bearing microspheres, effectiveness was assessed using safranine O (S.O) staining IF. Results Single-cell analysis suggested that synovium influences via exocrine release findings revealed purified enhanced antioxidant capacity chondrocytes, maintained matrix metabolism stability. S-EXO group showed significant reduction mitoROS ROS 164.2% ( P < 0.0001) 142.7% 0.0001), respectively, compared IL-1β group. Furthermore, exhibited increased COL II ACAN levels, increments 2.1-fold 3.1-fold over Additionally, decrease MMP13 ADAMTS5 protein expression 42.3% 44.4% respectively. It found S-EXO-containing microspheres could effectively deliver SOD3 significantly mitigate progression. OARSI score markedly decreased Conclusion demonstrated secreted fibroblasts exert protective effect on laden offer promising therapeutic alternative

Language: Английский

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Synovial mesenchymal stem cell-derived exosomal miR-485-3p relieves cartilage damage in osteoarthritis by targeting the NRP1-mediated PI3K/Akt pathway

Heliyon, Journal Year: 2024, Volume and Issue: 10(2), P. e24042 - e24042

Published: Jan. 1, 2024

Osteoarthritis (OA) is an age-related musculoskeletal disease that results in pain and functional disability. Stem cell therapy has been considered as a promising treatment for OA. In this study, the therapeutic action potential mechanism of synovial mesenchymal stem cells (SMSCs)-derived exosomes (Exos) OA cartilage damage were investigated. Cartilage stimulated with IL-1β to establish vitro model damage. functions detected by CCK-8, scratch assay, flow cytometry, respectively. Inflammatory cytokine levels assessed ELISA. Target molecule measured qRT‒PCR Western blotting. Exos-induced differential expression miRNAs analyzed microarray analysis. The interaction between miR-485-3p neuropilin-1 (NRP1) was validated dual luciferase reporter RIP assays. We found Exos promoted proliferation, migration, ECM secretion, but restrained apoptosis inflammation IL-1β-exposed via up-regulation miR-485-3p. Additionally, directly targeted NRP1 repress expression, which subsequently caused inactivation PI3K/Akt pathway. protective effect on counteracted overexpression-mediated activation conclusion, delivered attenuate IL-1β-induced degradation targeting succedent Our findings shed light novel OA, suggest restoration might be approach treatment.

Language: Английский

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Cemented vs. Cementless Fixation in Primary Knee Replacement: A Narrative Review

Materials, Journal Year: 2024, Volume and Issue: 17(5), P. 1136 - 1136

Published: Feb. 29, 2024

Knee osteoarthritis (OA) is one of the leading causes disability around globe. Osteoarthritis mainly considered a disease affecting elderly. However, more and studies show that sports overuse, obesity, or congenital disorders can initiate pathologic cascade leads to OA changes in younger population. Nevertheless, mostly affects elderly, with increasing life expectancy, will develop individuals. To date, golden standard treatment end-stage total joint replacement (TJR), which restores painless knee motion function. One weakest elements TJR its bonding bone, be achieved by material, such as poly methyl-methacrylate (PMMA), cementless fixation supported bone ingrowth onto endoprosthesis surface. Each technique has advantages; however, most important factor revision rate survivor time. In past, numerous articles were published regarding rate, but no consensus been established yet. this review, we focused on comparison cemented surgeries. We introduced PICO rules, including population, intervention, outcomes PubMed search. identified 783 between 2010 2023, out included 14 our review. Our review reveals there universally prescribed approach fixate prostheses. The determination suitable method necessitates an individualized decision-making process involving active participation informed consent each patient.

Language: Английский

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Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO‐1 pathway

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(7), P. 3352 - 3369

Published: April 20, 2024

Abstract Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes destruction. Cucurbitacin B (CuB) naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study to investigate potential role and mechanisms CuB mouse model OA. This identified key targets pathways through network pharmacology analysis. In vivo vitro studies confirmed Through pharmacology, 54 for treating OA were identified. therapeutic associated with nod‐like receptor pyrin domain 3 (NLRP3) inflammasome pyroptosis. Molecular docking results indicate strong binding affinity nuclear factor erythroid 2‐related 2 (Nrf2) p65. experiments demonstrate effectively inhibits expression pro‐inflammatory factors induced interleukin‐1β (IL‐1β), including cyclooxygenase‐2, inducible nitric oxide synthase, IL‐1β, IL‐18. degradation type II collagen aggrecan extracellular matrix (ECM), as well metalloproteinase‐13 disintegrin metalloproteinase thrombospondin motifs‐5. protects cells activating Nrf2/hemeoxygenase‐1 (HO‐1) pathway inhibiting factor‐κB (NF‐κB)/NLRP3 inflammasome‐mediated Moreover, show can slow down cartilage an model. prevents progression chondrocytes ECM degradation. action further mediated activation Nrf2/HO‐1 inhibit NF‐κB/NLRP3 activation. Thus, agent

Language: Английский

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Sipeimine ameliorates osteoarthritis progression by suppression of NLRP3 inflammasome-mediated pyroptosis through inhibition of PI3K/AKT/NF-κB pathway: An in vitro and in vivo study

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 46, P. 1 - 17

Published: May 1, 2024

Osteoarthritis (OA) is a chronic and degenerative condition that persists progresses over time. Sipeimine (Sip), steroidal alkaloid derived from Fritillariae Cirrhosae Bulbus, has attracted considerable attention due to its exceptional anti-inflammatory, analgesic, antioxidant, anti-cancer characteristics. However, Sip's effects on OA mechanism still need further research. This study utilized network pharmacology identify initial targets for Sip. Functional associations of Sip in were clarified through Gene Ontology (GO) enrichment analysis, bioinformatically analyzing list targets. Subsequently, Kyoto Encyclopedia Genes Genomes (KEGG) analysis assessed pathways linked therapeutic efficacy OA. Molecular docking techniques explored binding affinity with key In vitro experiments impact lipopolysaccharide (LPS)-induced pro-inflammatory factors protective collagen-II aggrecan degradation within the extracellular matrix (ECM). Western blotting fluorescence analyses conducted determine Sip-mediated signaling pathways. Moreover, vivo using mouse model validated efficacy. The results revealed total 57 candidate treatment. GO demonstrated robust correlation between inflammatory response, response LPS NF-κB-inducing kinase activity KEGG highlighted significance NF-κB PI3K-AKT potential Furthermore, molecular p65 PI3K. effectively suppressed expression induced by LPS, such as COX-2, iNOS, IL-1β, IL-18. Besides, counteracted ECM MMP-13 ADAMTS-5 mediated LPS. safeguarding ascribed inhibition PI3K/AKT/NF-κB pathway NLRP3 inflammasome pyroptosis. Additionally, could alleviate subchondral remodeling, cartilage degeneration, synovitis well exhibited attenuating progression suppressing pathway, consequently inhibiting activation translational this articleThis provides biological rationale use treatment, provide new concept targeted application natural compounds.

Language: Английский

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A meta-analysis and systematic review of the clinical efficacy and safety of platelet-rich plasma combined with hyaluronic acid (PRP + HA) versus PRP monotherapy for knee osteoarthritis (KOA)

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 17, 2025

KOA, a chronic degenerative joint disease, is commonly treated with intra-articular HA and PRP, used alone or in combination. However, the efficacy safety of combination therapy (PRP + HA) remain unclear. The aim this systematic review meta-analysis to assess clinical effectiveness profile PRP versus monotherapy for KOA. A search was conducted using four electronic databases (PubMed, EMBASE, Scopus, Cochrane Library) select publications published peer-reviewed journals. mean difference (MD) risk ratio (RR) calculated, along their 95% confidence intervals. We assessed heterogeneity Q I2statistics appropriate p-value. analysis RevMan 5.4. GRADE system evidence assessment each outcome parameter. This 11 RCTs (n = 1023 KOA patients) revealed that has substantial than reducing OMAC total scores [MD -1.77 (95% CI -2.20 − 1.34); I2 10%, p < 0.001], VAS -4.27 -4.96 3.58); 13%, Lequesne index score -5.48 -6.56 4.40); 16%, while increasing IKDC -2.10 -3.70 0.50); 9%, 0.01], low adverse events [RR 0.41 0.35 0.48); 12%, 0.001]. reveals that, patients safe yields better outcomes pain relief functional improvement compared monotherapy.

Language: Английский

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Efficacy and safety of mesenchymal stromal cell transplantation in the treatment of autoimmune and rheumatic immune diseases: a systematic review and meta-analysis of randomized controlled trials

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 11, 2025

This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in treatment autoimmune rheumatic immune diseases through randomized controlled trials (RCTs). Two researchers conducted a comprehensive search Chinese English databases from their inception until Dec. 2023. The literature screening data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. A total 42 relevant RCTs, involving 2,183 participants, ultimately included this study. These RCTs encompassed four types bone diseases, namely rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis, systemic sclerosis arthritis, lupus erythematosus (SLE), inflammatory bowel disease, multiple sclerosis, primary Sjögren's syndrome (PSS). systematic review indicates that MSC may improve RA, PSS. meta-analysis reveals significantly improved symptoms patients with OA [VAS (visual analogue scale): marrow: SMD = − 0.95, 95% CI 1.55 0.36, P 0.002; umbilical cord: 1.25, 2.04 0.46, adipose tissue: -1.26, -1.99 0.52, 0.0009)], SLE [Systemic disease activity index (SLEDAI): 2.32, 3.59 1.06, 0.0003], [clinical efficacy: RR 2.02, 1.53 2.67, < 0.00001]. However, not (Ssc). Importantly, did increase incidence adverse events (OA: 1.23, 0.93 1.65, 0.15; SLE: 0.83, 0.28 2.51, 0.76; Inflammatory disease: 0.99, 0.81 1.22, 0.96; Multiple sclerosis: 1.12, 1.53, 0.50), supporting its profile across studies. findings suggest holds promise for several while highlighting areas where further research is warranted. have potential treat diseases. Moreover. appears be relatively safe could considered as viable alternative option

Language: Английский

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Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 12, 2025

Bone-related diseases impact a large portion of the global population and, due to their high disability rates and limited treatment options, pose significant medical economic challenges. Mesenchymal stem cells (MSCs) can differentiate into multiple cell types offer strong regenerative potential, making them promising for treating various diseases. However, issues with immune response survival limit effectiveness transplantation. This has led increased interest in cell-free therapy, particularly use exosomes, which is most studied form this approach. Exosomes are extracellular vesicles that contain proteins, lipids, nucleic acids play key role communication material exchange. Pyroptosis, death involved innate immunity, also associated many Studies have shown MSC-derived exosomes therapeutic potential range conditions by regulating inflammation pyroptosis. study explored modulating pyroptosis improve bone-related

Language: Английский

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