Identification of a complex between fibronectin and aggrecan G3 domain in synovial fluid of patients with painful meniscal pathology.
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.
Scuderi
Gaetano J
GJ
Stanford University, Stanford, CA, USA.
Woolf
Naruewan
N
Dent
Kaitlyn
K
Golish
S Raymond
SR
Cuellar
Jason M
JM
Cuellar
Vanessa G
VG
Yeomans
David C
DC
Carragee
Eugene J
EJ
Angst
Martin S
MS
Bowser
Robert
R
Hanna
Lewis S
LS
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
D053674:Aggrecans; D015415:Biomarkers; D005353:Fibronectins; D007371:Interferon-gamma