HSPA4 and SYVN1 positivity in osteoarthritis synovium as indicators of proteostasis dysfunction.

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.