Parishin A-loaded mesoporous silica nanoparticles modulate macrophage polarization to attenuate tendinopathy DOI Creative Commons
Lisha Zhu, Yu Wang, Shanshan Jin

et al.

npj Regenerative Medicine, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 10, 2023

Macrophages are involved mainly in the balance between inflammation and tenogenesis during healing process of tendinopathy. However, etiological therapeutic strategies to efficiently treat tendinopathy by modulating macrophage state still lacking. In this study, we find that a small molecule compound Parishin-A (PA) isolated from Gastrodia elata could promote anti-inflammatory M2 polarization inhibiting gene transcription protein phosphorylation signal transducers activators 1. Local injection or sustained delivery PA mesoporous silica nanoparticles (MSNs) almost recover native tendon's dense parallel-aligned collagen matrix collagenase-induced macrophage-mediated immune microenvironment preventing heterotopic ossification. Especially, MSNs decrease doses PA, frequency yield preferable effects. Mechanistically, intervention with indirectly inhibit activation mammalian target rapamycin repress chondrogenic osteogenic differentiation tendon stem/progenitor cells influencing inflammatory cytokine secretion. Together, pharmacological natural small-molecule modulate status appears be promising strategy for treatment.

Language: Английский

Nitric Oxide Nanomotor Driving Exosomes-Loaded Microneedles for Achilles Tendinopathy Healing DOI
Anlong Liu, Qi Wang, Zinan Zhao

et al.

ACS Nano, Journal Year: 2021, Volume and Issue: 15(8), P. 13339 - 13350

Published: July 29, 2021

The microneedle (MN) provides a promising strategy for transdermal delivery of exosomes (EXO), in which the therapeutic effects and clinical applications are greatly reduced by fact that EXO can only partially reach injury site passive diffusion. Here, we designed detachable MN array to deliver modified nitric oxide nanomotor (EXO/MBA) Achilles tendinopathy (AT) healing. With releasing EXO/MBA, l-arginine was converted NOS or ROS as driving force. Benefiting from motion ability property MPC tending lower pH, could accumulate at more efficiently. This work demonstrated EXO/MBA-loaded notably suppressed inflammation AT, facilitated proliferation tendon cells, increased expression Col1a, prevented extracellular matrix degradation, indicating its potential value enthesiopathy healing other related biomedical fields.

Language: Английский

Citations

127
Psoriatic arthritis from a mechanistic perspective DOI
Georg Schett, Proton Rahman, Christopher T. Ritchlin

et al.

Nature Reviews Rheumatology, Journal Year: 2022, Volume and Issue: 18(6), P. 311 - 325

Published: May 5, 2022

Language: Английский

Citations

94
Psoriatic Arthritis: Pathogenesis and Targeted Therapies DOI Open Access
Ana Belén Azuaga, Julio Ramírez, Juan D. Cañete

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4901 - 4901

Published: March 3, 2023

Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated uveitis bowel (Crohn’s ulcerative colitis). To capture these manifestations as well the comorbidities, to recognize their underlining common pathogenesis, name of psoriatic was coined. The pathogenesis complex multifaceted, an interplay genetic predisposition, triggering environmental factors, activation innate adaptive immune system, although autoinflammation has been implicated. Research identified several immune-inflammatory pathways defined cytokines (IL-23/IL-17, TNF), leading development efficacious therapeutic targets. However, responses drugs occur different tissues involved, resulting challenge global management disease. Therefore, more translational research necessary order identify new targets improve current outcomes. Hopefully, this may become reality through integration omics technologies that allow better understanding relevant cellular molecular players In narrative review, we aim provide updated overview pathophysiology, including latest findings from multiomics studies, describe targeted therapies.

Language: Английский

Citations

76
Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity DOI
Yue Zhai, Liang Chen, Qian Zhao

et al.

Science, Journal Year: 2023, Volume and Issue: 379(6637)

Published: March 16, 2023

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, identified panel of cysteine residues differentially modified carboxyethylation required 3-hydroxypropionic acid generate patients with AS. The lysosomal degradation integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated peptides were presented HLA-DRB1*04 stimulate CD4+ T cell responses and induce autoantibody production. Immunization HLA-DR4 transgenic mice the ITGA2B-ceC96 peptide promoted colitis vertebral bone erosion. Thus, metabolite-induced give rise pathogenic lead autoreactive production autoimmune diseases.

Language: Английский

Citations

48
Hierarchical helical carbon nanotube fibre as a bone-integrating anterior cruciate ligament replacement DOI

Liyuan Wang,

Fang Wan, Yifan Xu

et al.

Nature Nanotechnology, Journal Year: 2023, Volume and Issue: 18(9), P. 1085 - 1093

Published: May 4, 2023

Language: Английский

Citations

44
A textile magnetoelastic patch for self-powered personalized muscle physiotherapy DOI Creative Commons
Jing Xu, Trinny Tat, Junyi Yin

et al.

Matter, Journal Year: 2023, Volume and Issue: 6(7), P. 2235 - 2247

Published: June 27, 2023

Language: Английский

Citations

43
Biological classification of childhood arthritis: roadmap to a molecular nomenclature DOI
Peter A. Nigrović, Robert A. Colbert, V. Michael Holers

et al.

Nature Reviews Rheumatology, Journal Year: 2021, Volume and Issue: 17(5), P. 257 - 269

Published: March 17, 2021

Language: Английский

Citations

98
Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression DOI Creative Commons
‬‬‬‬Abdulla Watad, Hannah Rowe, Tobias Russell

et al.

Annals of the Rheumatic Diseases, Journal Year: 2020, Volume and Issue: 79(8), P. 1044 - 1054

Published: May 13, 2020

The human enthesis conventional T cells are poorly characterised.To study the biology of in enthesis.CD4+ and CD8+ were investigated 25 samples using immunofluorescence, cytometrically, bulk RNAseq quantitative real-time PCR following anti-CD3/CD28 bead stimulation to determine interleukin (IL)-17A tumour necrosis factor (TNF) levels. T-cell receptor (TCR) repertoires characterised a search for putative reactivity was carried out TCR3 database. impact pharmacological antagonism with retinoic acid receptor-related orphan nuclear gamma t inhibitor (RORγti), methotrexate phosphodiesterase type 4 (PDE4i) investigated.Immunofluorescence cytometry suggested entheseal resident CD4+ memory phenotype (CD69+/CD45RA-) tissue residency gene transcripts (higher NR4A1/AhR lower KLF2/T-bet transcripts). Both showed increased expression immunomodulatory genes including IL-10 TGF-β compared peripheral blood having higher CD103, CD49a SIPR1 transcript that matched cells. Following stimulation, produced more TNF than IL-17A exclusively by both Cytomegalovirus influenza A virus clonotype reactivity. production from effectively inhibited PDE4i, while RORγti only reduced secretion.Healthy exhibit regulatory characteristics predicted antiviral expressing levels suggestive residency. Inducible can be robustly vitro.

Language: Английский

Citations

72
A Self‐Powered Piezo‐Bioelectric Device Regulates Tendon Repair‐Associated Signaling Pathways through Modulation of Mechanosensitive Ion Channels DOI Creative Commons
Marc Fernández, Alexandre Trotier,

Seçil Demir

et al.

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(40)

Published: Aug. 23, 2021

Abstract Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome limitations current tendon grafting approaches, bioelectronic therapies show promise treating musculoskeletal diseases, accelerating functional recovery through activation tissue regeneration‐specific signaling pathways. Self‐powered devices, particularly piezoelectric materials, represent paradigm shift biomedicine, negating for battery or external powering complementing existing mechanotherapy accelerate repair processes. Here, dynamic response cells collagen‐analogue scaffold comprised aligned nanoscale fibers made ferroelectric material poly(vinylidene fluoride‐ co ‐trifluoroethylene) is shown. It demonstrated that motion‐powered electromechanical stimulation piezo‐bioelectric device results ion channel modulation vitro regulates specific regeneration Finally, potential piezo‐bioelectronic modulating progression tendinopathy‐associated processes vivo, using rat Achilles acute injury model This study indicates mechanosensitive sensitivity promotes tendon‐specific over non‐tenogenic

Language: Английский

Citations

66
Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis DOI Creative Commons
Shengqian Dou, Qun Wang, Bin Zhang

et al.

Cell Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: July 12, 2022

Keratoconus is a common ectatic corneal disorder in adolescents and young adults that can lead to progressive visual impairment or even legal blindness. Despite the high prevalence, its etiology not fully understood. In this study, we performed single-cell RNA sequencing (scRNA-Seq) analysis on 39,214 cells from central corneas of patients with keratoconus healthy individuals, define involvement each cell type during disease progression. We confirmed role stromal disease, where dysregulation collagen extracellular matrix (ECM) occurred. Differential gene expression histological analyses revealed two potential novel markers for cells, namely CTSD CTSK. Intriguingly, detected elevated levels YAP1 TEAD1, master regulators biomechanical homeostasis, cells. Cyclical mechanical experiments implicated stretch prompting protease production epithelial corneas, observed reduced basal abnormally differentiated superficial unraveling lesions were usually neglected clinical diagnosis. addition, several cytokines immune samples supported inflammatory response progression keratoconus. Finally, dysregulated cell-cell communications keratoconus, found only few ligand-receptor interactions gained but large fraction interactional pairs was erased especially those related inhibition anti-inflammatory process. Taken together, study facilitates understanding molecular mechanisms underlying pathogenesis, providing insights into diagnosis interventions.

Language: Английский

Citations

55