Highlights
- •Detailed clinical, histology and expression data from 33 patients was triangulated.
- •Synovial gene expression profiles from knee OA and two non-OA injuries are reported.
- •OA risk factors BMI and gender, impact the significance of synovial gene expression.
- •UPR is the top up-regulated pathway in OA synovium.
- •ER-associated degradation pathway component SYVN1 may be therapeutic target for OA.
Abstract
Background
Gene expression in healthy synovium remains poorly characterised. Thus, synovial functional
activity changes associated with osteoarthritis (OA) are difficult to define. This
study sought to identify differentially expressed genes (DEG) of end-stage OA and
assess the influence of OA risk factors on these DEG.
Methods
Anonymised patient clinical data and x-ray images were analysed. Osteoarthritic and
non-osteoarthritic patients with soft tissue or traumatic knee injuries were matched
for body mass index (BMI) and sex. Tissue samples were partitioned for immunocytochemistry
(IHC) and microarray analysis. Multiple bioinformatics applications were utilised
to determine changes in functional and canonical pathway activation.
Results
Age, disease-modifying injections and hypertension were confounding factors between
patient groups. Inflammation was present in all tissues. Cartilage debris and inflammatory
aggregates were noted in many osteoarthritic patient tissues. IHC and expression analyses
revealed upregulation of synoviolin 1 (SYVN1) in osteoarthritic synovium. Significant
differential expression was noted in 2084 genes. Osteoarthritic synovium displayed
a significant upregulation of 95% of DEG coding for proteins, relative to non-osteoarthritic
synovium tissues. Unfolded protein response (UPR)-related genes were upregulated in
osteoarthritic synovium; gene expression of molecules within many canonical pathways
including protein ubiquitination and UPR pathways was modified by BMI and sex.
Conclusions
The synovium of all three pathologies exhibited elements of an inflammatory response.
Cartilage debris, age, BMI and sex influence DEG of osteoarthritic synovium. UPR pathway
is the top deregulated canonical pathway identified in osteoarthritic synovium regardless
of BMI and sex, while typical OA-associated inflammatory and matrix gene responses
were minimal.
Keywords
Abbreviations:
BM (Base Model), BMI (body mass index), DEG (differentially expressed genes), IHC (immunohistochemistry), IM (Improved Model), IM-OATKR (Improved Model-OA total knee replacement), IPA (Ingenuity pathway analysis), OATKR (OA total knee replacement), PCA (Principal component analysis), SF-12 Ph (The Short Form 12 physical score), SF-12 M (The Short Form 12 mental score), SYVN1 (synoviolin), WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 06, 2022
Accepted:
May 9,
2022
Received in revised form:
March 17,
2022
Received:
July 9,
2021
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
