dc.contributor.author | Thomas, B | |
dc.contributor.author | Montero Melendez, T | |
dc.contributor.author | Oggero, S | |
dc.contributor.author | Kaneva, M | |
dc.contributor.author | Chambers, D | |
dc.contributor.author | Pinto, A | |
dc.contributor.author | Nerviani, A | |
dc.contributor.author | Lucchesi, D | |
dc.contributor.author | Austin-Williams, S | |
dc.contributor.author | HUSSAIN, M | |
dc.contributor.author | Allen, B | |
dc.contributor.author | Pitzalis, C | |
dc.contributor.author | Malcangio, M | |
dc.contributor.author | Dell’Accio, F | |
dc.contributor.author | Norling, L | |
dc.contributor.author | Perretti, M | |
dc.date.accessioned | 2024-08-09T09:59:20Z | |
dc.date.available | 2024-07-10 | |
dc.date.available | 2024-08-09T09:59:20Z | |
dc.date.issued | 2024-07-23 | |
dc.identifier.issn | 2326-5191 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/98715 | |
dc.description.abstract | Objective
This study was undertaken to establish the potential therapeutic profile of neutrophil-derived extracellular vesicles (EVs) in experimental inflammatory arthritis and associate pharmacological activity with specific EV components, focussing on microRNAs.
Methods
Neutrophil EVs were administered intra-articularly through a prophylactic or therapeutic protocol to male C57BL/6 mice undergoing serum-transfer induced inflammatory arthritis. Transcriptomic analysis of knees was performed on joints following EV administration, Naïve and arthritic mice (untreated), n=4/group, and EV-treated diseased mice (intra-articular administration) with contralateral (vehicle-treated) n=8/group. Comparison of healthy donor and rheumatoid arthritis (RA) patient neutrophil EVs was performed.
Results
EVs afforded cartilage protection with an increase in Collagen-II and reduced Collagen-X expression within the joint. To gain mechanistic insights, RNA sequencing of the arthritic joints was conducted. A total of 5,231 genes were differentially expressed (P<0.05), with 257 unique to EV treatment. EVs affected key regenerative pathways involved in joint development, including Wnt and Notch signalling. This wealth of genomic alteration prompted to identify microRNAs in EVs, 10 of which are associated with RA. As a proof-of-concept, we focused on miR-455-3p, which was detected in both healthy donor and RA EVs. EV addition to chondrocyte cultures elevated miR-455-3p and exerted anti-catabolic effects upon IL-1β stimulation; these effects were blocked by actinomycin or miR-455-3p antagomir.
Conclusion
Neutrophils from RA patients yielded EVs with composition, efficacy and miR-455-3p content similar to those of healthy volunteers, suggesting that neutrophil EVs could be developed as an autologous treatment to protect and repair joint tissue of patients affected by inflammatory arthritides. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.relation.ispartof | Arthritis & Rheumatology | |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | |
dc.title | Molecular determinants of neutrophil extracellular vesicles that drive cartilage regeneration in inflammatory arthritis | en_US |
dc.type | Article | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Accepted | en_US |
pubs.publisher-url | http://dx.doi.org/10.1002/art.42958 | |
dcterms.dateAccepted | 2024-07-10 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Reprogramming Resolution in the Arthritic Joint::Versus Arthritis | en_US |
qmul.funder | Reprogramming Resolution in the Arthritic Joint::Versus Arthritis | en_US |