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Molecular expression patterns in the synovium and their association with advanced symptomatic knee osteoarthritis

Wyatt, Laura A.; Nwosu, Lilian N.; Wilson, Deborah; Hill, Roger; Spendlove, Ian; Bennett, Andrew J.; Scammell, Brigitte E.; Walsh, David A.


Clinical Trial Manager

Lilian N. Nwosu

Deborah Wilson

Roger Hill

Brigitte E. Scammell

Professor of Rheumatology


Objective: Osteoarthritis (OA) is a major source of knee pain. Mechanisms of OA knee pain are incompletely understood but include synovial pathology. We aimed to identify molecular expression patterns in the synovium associated with symptomatic knee OA.
Design: Snap frozen synovia were from people undergoing total knee replacement (TKR) for advanced OA, or from post-mortem (PM) cases who had not sought help for knee pain. Associations with OA symptoms were determined using discovery and validation samples, each comprising TKR and post mortem (PM) cases matched for chondropathy (Symptomatic or Asymptomatic Chondropathy). Associations with OA were determined by comparing age matched TKR and PM control cases. Real-time quantitative PCR for 96 genes involved in inflammation and nerve sensitisation used TaqMan® Array Cards in discovery and validation samples, and protein expression for replicated genes was quantified using Luminex bead assay.
Results: Eight genes were differentially expressed between asymptomatic and symptomatic chondropathy cases and replicated between discovery and validation samples (P3-fold change). Of these, matrix metalloprotease (MMP)-1 was also increased whereas interleukin-1 receptor 1 (IL1R1) and vascular endothelial growth factor (VEGF) were decreased at the protein level in the synovium of symptomatic compared to asymptomatic chondropathy cases. MMP1 protein expression was also increased in OA compared to PM controls.
Conclusion: Associations of symptomatic OA may suggest roles of MMP1 expression and IL1R1 and VEGF pathways in OA pain. Better understanding of which inflammation-associated molecules mediate OA pain should inform refinement of existing therapies and development of new treatments.


Wyatt, L. A., Nwosu, L. N., Wilson, D., Hill, R., Spendlove, I., Bennett, A. J., …Walsh, D. A. (2018). Molecular expression patterns in the synovium and their association with advanced symptomatic knee osteoarthritis. Osteoarthritis and Cartilage, 27(4), 667-675.

Journal Article Type Article
Acceptance Date Dec 19, 2018
Online Publication Date Dec 28, 2018
Publication Date Dec 28, 2018
Deposit Date Jan 14, 2019
Publicly Available Date Dec 29, 2019
Journal Osteoarthritis and Cartilage
Print ISSN 1063-4584
Electronic ISSN 1522-9653
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 27
Issue 4
Pages 667-675
Keywords Rheumatology; Orthopedics and Sports Medicine; Biomedical Engineering
Public URL
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