title: Association of synovial inflammation and inflammatory mediators with glenohumeral rotator cuff pathology.
abstract: OBJECTIVE
  We hypothesized that patients with full-thickness rotator cuff tears would have greater synovial inflammation compared with those without rotator cuff tear pathology, with gene expression relating to histologic findings.
  
  
  METHODS
  Synovial sampling was performed in 19 patients with full-thickness rotator cuff tears (RTC group) and in 11 patients without rotator cuff pathology (control group). Cryosections were stained and examined under light microscopy and confocal fluorescent microscopy for anti-cluster CD45 (common leukocyte antigen), anti-CD31 (endothelial), and anti-CD68 (macrophage) cell surface markers. A grading system was used to quantitate synovitis under light microscopy, and digital image analysis was used to quantify the immunofluorescence staining area. Quantitative polymerase chain reaction was performed for validated inflammatory markers. Data were analyzed with analysis of covariance, Mann-Whitney U, and Spearman rank order testing, with significance set at α = .05.
  
  
  RESULTS
  The synovitis score was significantly increased in the RTC group compared with controls. Immunofluorescence demonstrated significantly increased staining for CD31, CD45, and CD68 in the RTC vs control group. CD45+/68- cells were found perivascularly, with CD45+/68+ cells toward the joint lining edge of the synovium. Levels of matrix metalloproteinase-3 (MMP-3) and interleukin-6 were significantly increased in the RTC group, with a positive correlation between the synovitis score and MMP-3 expression.
  
  
  CONCLUSIONS
  Patients with full-thickness rotator cuff tears have greater levels of synovial inflammation, angiogenesis, and MMP-3 upregulation compared with controls. Gene expression of MMP-3 correlates with the degree of synovitis.
authors.affiliation: Department of Orthopedic Surgery, Stanford University, Stanford, CA, USA; VA Palo Alto Healthcare System, Palo Alto, CA, USA. Electronic address: gabrams@stanford.edu.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Abrams
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, CA, USA.
authors.forename: Ayala
authors.initials: A
authors.lastname: Luria
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, CA, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Carr
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Rhodes
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, CA, USA; Division of Immunology/Rheumatology, Stanford University, Stanford, CA, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, CA, USA; Division of Immunology/Rheumatology, Stanford University, Stanford, CA, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D015850:Interleukin-6 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000235:genetics; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D000070636:Rotator Cuff Injuries / Q000150:complications*; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000737:chemistry / Q000473:pathology; D013585:Synovitis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; D017493:Leukocyte Common Antigens; D019278:Matrix Metalloproteinase 3; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C511768:MMP3 protein, human
keywords: MMP; Rotator cuff; cytokine; inflammation; synovitis; synovium