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The Natural History of the Anterior Cruciate Ligament-Deficient Knee

Changes in Synovial Fluid Cytokine and Keratan Sulfate Concentrations

Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Andreas Buchgraber, MD

University of Heidelberg School of Medicine, Zentrum für Sporttraumatologie und Gelenkchirurgie, Heidelberg, Germany

Hans Passler, MD

University of Heidelberg School of Medicine, Zentrum für Sporttraumatologie und Gelenkchirurgie, Heidelberg, Germany

Molly Vogt, PhD

Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Eugene Thonar, PhD

Department of Biochemistry, Rush Presbyterian School of Medicine, Chicago, Illinois

Freddie Fu, MD

Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Christopher H. Evans, PhD

Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Restoring knee stability through reconstruction, while providing symptomatic relief, has not been shown to decrease the incidence of degenerative changes after rupture of the anterior cruciate ligament. This suggests that posttraumatic osteoarthritis may not be purely bio mechanical in origin, but also biochemical. To test this, we measured the levels of seven cytokine modulators of cartilage metabolism in knee joint synovial fluid after anterior cruciate ligament rupture. We also measured keratan sulfate, a product of articular cartilage catab olism. The sample population consisted of patients with uninjured knee joints (N = 10), and patients with acute ( N = 60), subacute (N = 18), and chronic (N = 8) anterior cruciate ligament-deficient knees. Synovial fluid samples were analyzed by enzyme-linked immu nosorbent assays. Normal synovial fluids contained high levels of the interleukin-1 receptor antagonist but low concentrations of other cytokines. Immediately af ter ligament rupture there were large increases in in terleukins 6 and 8, tumor necrosis factor , and keratan sulfate. Interleukin-1 levels remained low throughout the course. As the injury became subacute and then chronic, interleukin-6, tumor necrosis factor-, and keratan sulfate levels fell but remained considerably elevated 3 months after injury. Concentrations of inter leukin-1Ra fell dramatically. Granulocyte-macrophage colony-stimulating factor concentrations were normal acutely and subacutely but by 3 months after injury were elevated 10-fold. Our data reveal a persistent and evolving disturbance in cytokine and keratan sulfate profiles within the anterior cruciate ligament-deficient knee, suggesting an important biochemical dimension to the development of osteoarthritis there.

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