title: Identification of a complex between fibronectin and aggrecan G3 domain in synovial fluid of patients with painful meniscal pathology.
abstract: OBJECTIVE
  We previously described a panel of four cytokines biomarkers in knee synovial fluid for acute knee pain associated with meniscal pathology. The cytokine biomarkers included interferon gamma (IFN-gamma), interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1beta). Validation studies using other immunologic techniques confirmed the presence of IL-6, MCP-1 and MIP-1beta, but not IFN-gamma. Therefore we sought the identity of the IFN-gamma signal in synovial fluid.
  
  
  METHODS
  Knee synovial fluid was collected from patients with an acute, painful meniscal injury, as well as asymptomatic volunteers. A combination of high-pressure chromatography, mass spectrometry and immunological techniques were used to enrich and identify the protein components representing the IFN-gamma signal.
  
  
  RESULTS
  A protein complex of fibronectin and the aggrecan G3 domain was identified in the synovial fluid of patients with a meniscal tear and pain that was absent in asymptomatic controls. This protein complex correlated to the IFN-gamma signal. A novel enzyme-linked immunosorbent assay (ELISA) was developed to specifically identify the complex in synovial fluid.
  
  
  CONCLUSIONS
  We have identified a protein complex of fibronectin and aggrecan G3 domain that is a candidate biomarker for pain associated with meniscal injury.
authors.affiliation: Stanford University, Stanford, CA, USA.
authors.forename: Gaetano J
authors.initials: GJ
authors.lastname: Scuderi
authors.forename: Naruewan
authors.initials: N
authors.lastname: Woolf
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Dent
authors.forename: S Raymond
authors.initials: SR
authors.lastname: Golish
authors.forename: Jason M
authors.initials: JM
authors.lastname: Cuellar
authors.forename: Vanessa G
authors.initials: VG
authors.lastname: Cuellar
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Carragee
authors.forename: Martin S
authors.initials: MS
authors.lastname: Angst
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
authors.forename: Lewis S
authors.initials: LS
authors.lastname: Hanna
mesh_terms: D000293:Adolescent; D000328:Adult; D053674:Aggrecans / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D013058:Mass Spectrometry; D008592:Menisci, Tibial / Q000737:chemistry / Q000473:pathology*; D011446:Prospective Studies; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000276:immunology; D013582:Synovial Fluid / Q000737:chemistry*; D055815:Young Adult
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D005353:Fibronectins; D007371:Interferon-gamma