Full Papers
HSPA4 and SYVN1 positivity in osteoarthritis synovium as indicators of proteostasis dysfunction
M.M. Roebuck1, J. Jamal2, A. Wood3, A.J. Santini4, B. Lane5, G. Bou-Gharios6, S.P. Frostick7, P.-F. Wong8
- Department of Musculoskeletal & Ageing Science, Institute of Life Course & Medical Sciences, University of Liverpool; and Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, UK.
- Department of Musculoskeletal & Ageing Science, Institute of Life Course & Medical Sciences, The University of Liverpool, UK; and Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
- Department of Musculoskeletal & Ageing Science, Institute of Life Course & Medical Sciences, University of Liverpool, UK.
- Liverpool University Hospitals NHS Foundation Trust, Liverpool; and Faculty of Health and Life Science, The University of Liverpool, UK.
- Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, UK.
- Department of Musculoskeletal & Ageing Science, Institute of Life Course & Medical Sciences, University of Liverpool, UK.
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, UK.
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia. wongpf@um.edu.my
CER19226
Full Papers
PMID: 41678149 [PubMed]
Received: 21/08/2025
Accepted : 12/01/2026
In Press: 12/02/2026
Abstract
OBJECTIVES:
To characterise two endoplasmic reticulum (ER) stress markers, HSPA4 and SYVN1, in knee synovium from osteoarthritis (OA) patients and two non-osteoarthritic cohorts undergoing arthroscopic (scope) or trauma surgery.
METHODS:
H & E and immunohistological staining with digital image analysis of whole tissue, intimal and sub-intimal layers was undertaken. Patient’s OA risk factors, health and functional status were scored using validated questionnaires and their contribution to changes in synovial cellular composition determined.
RESULTS:
Inflammatory cell infiltration and angiogenesis were highest in OA synovium. Increased small blood vessels in trauma tissues compared to OA suggested a continuum of remodelling responses from acute injury to OA. Adipocyte hyperplasia and hypertrophy, influenced by dyslipidaemia, were highest in OA synovium indicating metabolic stresses. HSPA4 and SYVN1 positivity was highest and mutually correlated in OA. OA SYVN1 positivity correlated with all inflammatory cells, vessels, synovitis, BMI and symptom duration. OA HSPA4 positivity correlated with CD3, vimentin and KL grade.
CONCLUSIONS:
Enhanced HSPA4 and SYVN1 positivity indicates extensive activation of protein quality control processes in OA synovium.
