title: Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints.
abstract: 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 alpha (TNFalpha) and interleukin 1beta (IL1beta) 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 kappa 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
authors.affiliation: Rheumatology Research Unit, Repatriation General Hospital and Department of Immunology, Allergy and Arthritis, Flinders Medical Centre, Adelaide, South Australia. malcolm.smith@rgh.sa.gov.au
authors.forename: M D
authors.initials: MD
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Barg
authors.forename: H
authors.initials: H
authors.lastname: Weedon
authors.forename: V
authors.initials: V
authors.lastname: Papengelis
authors.forename: T
authors.initials: T
authors.lastname: Smeets
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
authors.forename: M
authors.initials: M
authors.lastname: Kraan
authors.forename: M
authors.initials: M
authors.lastname: Coleman
authors.forename: M J
authors.initials: MJ
authors.lastname: Ahern
mesh_terms: D000293:Adolescent; D000328:Adult; D001182:Arthroscopy; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007719:Knee Joint / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins / Q000378:metabolism; D013583:Synovial Membrane / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D006023:Glycoproteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; C506030:TNFRSF11B protein, human