Interleukin-7 levels in synovial fluid increase with age and MMP-1 levels decrease with progression of osteoarthritis.
OBJECTIVE
Little is known about biochemical mediators that correlate with the initiation and progression of knee osteoarthritis (OA). We therefore valuated the roles of cytokines and metalloenzymes in knee OA in relation to OA grading, age, and BMI.


METHODS
A multiplex ELISA-based immunoassay (Luminex technology) was used to measure biochemical mediators in the synovial fluid (SF) of 82 patients undergoing knee surgery. All patients were classified according to age, BMI, and OA grade. 24 patients had no signs of OA (knee reconstruction surgeries). The mediators that were tested for included interleukins (IL-1Ra, IL-6, IL-7, and IL-18), chemokines (CCL2 (MCP-1), CCL3 (MIP-1a), and CXCL8 (IL-8)), growth factors (HGF and VEGF), and matrix metalloproteinases (MMP-1, MMP-2, MMP-9, and MMP-13).


RESULTS
There was a correlation between IL-7 levels in SF and age (p < 0.01). The 11 highest IL-7 levels were seen in patients who were aged between 59 and 72 but had different OA grades. In contrast, all patients who had severe OA in all 3 knee compartments (pan-OA) had only low or medium IL-7 levels. There was a negative correlation between MMP-1 levels in synovial fluid and grade of OA (p < 0.001). Correlation studies between pairs of mediators revealed two groups of mediators that are important in OA progression, dominated by MCP-1 and IL-1Ra.


CONCLUSIONS
IL-7 levels in SF are elevated in elderly people suffering from OA of different grades, but they are depressed in patients with severe 3-compartment OA, possibly due to widely impaired chondrocytes embedded in the affected cartilage tissue. The observed decrease in MMP-1 levels in SF, which is dependent on the severity of OA, may be caused by deterioration of superficial cartilage layers during progression of OA.
Department of Trauma Surgery, Plastic and Reconstructive Surgery, Georg-August University, Goettingen, Germany.
René
R
Rübenhagen
Jan Philipp
JP
Schüttrumpf
Klaus Michael
KM
Stürmer
Karl-Heinz
KH
Frosch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016922:Cellular Senescence; D018932:Chemokine CCL2 / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D015850:Interleukin-6; D015851:Interleukin-7; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases; D020781:Matrix Metalloproteinase 1