EXTENDED REPORT

Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints

M D Smith¹, E Barg², H Weedon¹, V Papengelis¹, T Smeets², P P Tak², M Kraan², M Coleman¹, M J Ahern¹

¹ Rheumatology Research Unit, Repatriation General Hospital and Department of Immunology, Allergy and Arthritis, Flinders Medical Centre, Adelaide, South Australia
² Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands

Correspondence to:
Correspondence to:
Professor M D Smith, Rheumatology Research Unit, Repatriation General Hospital, Daws Road, Daw Park, South Australia 5041;
malcolm.smith{at}rgh.sa.gov.au

Background: Synovial biopsies are used to study synovial immunopathology and are increasingly applied for the evaluation of new therapeutic strategies in chronic arthritis. Therefore, it is essential to be informed on the complete spectrum of synovial immunopathology.

Objective: To describe the cellular content, cytokine and cell adhesion molecule expression in synovial tissue from clinically and arthroscopically normal knees.

Methods: Synovial tissue was obtained from 20 normal subjects at the time of knee joint arthroscopy for unexplained knee pain. Tissue sections were studied for basic histopathology and for a range of cell surface markers, cytokines, and cell adhesion molecules by immunoperoxidase staining. Stained sections were evaluated by semiquantitative scoring and digital image analysis.

Results: Normal synovial tissue is composed predominantly of fibrofatty areolar tissue, with a variable thickness of intimal lining, composed of both CD68 positive macrophages and CD55 positive fibroblast-like synoviocytes. Interleukin 1 receptor antagonist (IL1Ra) was frequently detected in the synovial membrane of normal subjects (mean (SD) integrated optical density (IOD)=3809.6 (3893.9)), but both tumour necrosis factor (TNF) and interleukin 1ß (IL1ß) were rarely detected. In addition, cell adhesion molecules were rarely detected in the normal synovial membrane, with the exception of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Osteoprotegerin (OPG) expression was abundant on synovial lining macrophages (mean (SD) IOD=5276 (4716) as well as endothelial cells (mean (SD) IOD=557 (226)), but receptor activator of nuclear factor ligand (RANKL) expression was rarely seen.

Conclusions: The normal synovial membrane has a variable architecture, including thickness of the lining and the subintimal cell infiltrate, with little inflammatory cytokine production or expression of cell adhesion molecules. The excess of OPG expression over RANKL and IL1Ra over IL1 may be important for protection against joint damage

Keywords: synovial tissue; knee; microarchitecture

Abbreviations: ICAM-1, intercellular adhesion molecule-1; IL, interleukin; OPG, osteoprotegerin; IL1Ra, interleukin 1 receptor antagonist; RA, rheumatoid arthritis; RANKL, receptor activator of nuclear factor B ligand; TNF, tumour necrosis factor ; VCAM-1, vascular cell adhesion molecule-1

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