Increased levels of proteoglycan fragments in knee joint fluid after injury

Self Cite

234

165

Objective. To determine concentrations of crosslinked C-telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) from patients with joint injury, osteoarthritis (OA), or other knee arthritides.Methods. Two study groups were used: a crosssectional group, which included healthy-knee volunteers (reference group [REF]) and patients with pseudogout (PPA), an anterior cruciate ligament tear with or without a meniscus tear (INJ), or primary knee OA (POA); and a longitudinal group, which included patients with arthroscopic cartilage changes or septic arthritis. CTX-II was quantified by competition enzyme-linked immunosorbent assay (ELISA) based on a monoclonal antibody that recognized the C-terminus of the peptide EKGPDP as a proteolytic neoepitope. Aggrecan fragments, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were determined by ELISAs.Results. Concentrations of CTX-II in SF were higher in patients with PPA, INJ, and POA than in the REF group (P < 0.001). After joint injury, mean levels of CTX-II in SF were increased above REF levels at all time intervals (P < 0.001), and were highest within hours after trauma. In those in the longitudinal study group with joint cartilage damage, variation coefficients for CTX-II were 81% (between patients) and 64% (within patient), monitored over 1 year. In a patient with septic arthritis, SF CTX-II increased at the onset of symptoms, and peaked 30-fold higher than the baseline. Concentrations of all biomarkers decreased with successful treatment.Conclusion. This is the first report to describe the release into SF of soluble molecular fragments specific for the degradation of mature, crosslinked, type II collagen (CII) in human OA and joint injury. The results provide strong evidence that the integrity of the CII network of cartilage is compromised soon after joint injury and in arthritis. This early degradation of CII may represent an important treatment target.Osteoarthritis (OA) and joint injury are characterized by remodeling and degradation of cartilage, bone, and other joint tissues. The normally very slow turnover rate of cartilage matrix (1) is increased, as observed by several techniques in both animal OA models and human OA. Phasic changes in both synthesis and degradation of collagen and other matrix molecules (2-6) are associated with altered tissue structure and material properties (7-9).Increased joint tissue turnover after injury and in OA can be detected by a release of molecules and molecular fragments into synovial fluid (SF), blood, and urine. For example, the stimulated synthesis of type II collagen (CII) results in higher levels of CII C-propeptide in SF (10,11). Stimulated aggrecan synthesis results in more aggrecan fragments carrying the 846 epitope (12). Higher synovial concentrations of matrix metalloproteinases (MMPs), such as MMP-1 and MMP-3, and proteinase activity after joint injury and in OA are consistent with the observed expression of these

Section: Methodssupporting

confidence: 92%

Section: Methodssupporting

confidence: 90%

Section: Ctx-ii Concentrations Inmentioning

confidence: 66%

mentioning

confidence: 99%

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The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis

Lohmander¹,

Atley²,

Pietka³

et al. 2003

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234

165

“…Since the synovial cavity is a space from which molecules can clear, it is likely that stromelysin and collagenase are synthesized at a high rate within the joint, in order to reach the levels detected in the S F by ELISA. In addition, it has been documented both in patients with inflammatory arthritis (27) and in patients with traumatic injury (26) that there is a significant increase in the level of proteoglycan fragments in the SF. It would be interesting to compare the levels of these markers with the metalloproteinase levels to determine whether there is a correlation.…”

Section: Discussionmentioning

confidence: 99%

Detection of Stromelysin and Collagenase in Synovial Fluid From Patients with Rheumatoid Arthritis and Posttraumatic Knee Injury

Walakovits

Moore

Bhardwaj

et al. 1992

245

136

Objective. To quantify stromelysin and collagenase in synovial fluid (SF) from patients with rheumatoid arthritis (RA) or traumatic knee injury.Methods. Stromelysin and collagenase were measured in the SF of 33 patients with RA or pttraumatic knee injury, using specific double-antibody sandwich enzyme-linked immunosorbent assays. Stromelysin was fractionated from representative SF, and the molecular form was identilied by immunoblot analysis.Results. The stromelysin concentration was -20-fold higher than the collagenase concentration in the fluids from patients with RA and -8-fold higher in the fluids from patients with traumatic iaury. For both metalloproteinases, there was a higher enzyme concentration in RA SF than in the SF from patients with trauma (stromelysin 40.1 f 26 pg/ml [mean f SDI in RA SF, 8.5 +: 15 d m l in trauma SF; collagenase 2.2 f 3.3 pg/ml in RA SF, 1.1 f 2.3 pg/ml in trauma SF).The majority of the stromelysin within the SF bound to reactive red-agarose and was identified as prostrome-

Relationship of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover: Analyses of synovial fluid from patients with osteoarthritis

Ishiguro¹,

Ito²,

H³

et al. 1999

100

Objective. To determine the relationship between matrix metalloproteinases (MMPs), their inhibitors, and the turnover of matrix molecules in articular cartilage from patients with osteoarthritis (OA).Methods. Synovial fluid samples were collected from the knees of 54 patients with OA. Radiographic evaluations and magnetic resonance imaging were performed on the knees of 34 OA patients to classify the stage of the disease. Biochemical analyses and immunoassays were used to measure the concentrations of MMP-1, MMP-3, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, the disaccharide of hyaluronic acid, the proteoglycan glycosaminoglycan disaccharides of chondroitin 4-sulfate (⌬di-CS4) and chondroitin 6-sulfate (⌬di-CS6), the 846 epitope on chondroitin sulfate of cartilage proteoglycan aggrecan (putative biosynthetic marker), the keratan sulfate (KS) epitope of aggrecan (putative degradation marker), and the C-propeptide of cartilage type II procollagen (CPII) (biosynthetic marker).Results. The concentration of TIMP-1 was directly correlated with the levels of MMP-1 and MMP-3 (both were also correlated with each other), confirming earlier results. There was an inverse correlation between the ⌬di-CS6:⌬di-CS4 ratio and the concentration of MMP-3. The level of ⌬di-CS6 was correlated with that of the KS epitope, and to a lesser degree, with that of the 846 epitope (the latter was also correlated with the level of ⌬di-CS4). The concentration of TIMP-1 correlated with that of the 846 epitope, whereas TIMP-2 levels correlated with those of CPII. There were significantly lower concentrations of ⌬di-CS6, ⌬di-CS4, the 846 epitope, and CPII in synovial fluid from patients with late-stage OA.Conclusion. These observations suggest a link between proteolysis and inhibitor concentrations in OA cartilage. Production of TIMPs appears to be individually linked to the synthesis of specific cartilage molecules. The reduction in the amount of cartilage-matrix structural components suggests that there is a measurable loss of cartilage in the late stages of the disease, as suggested previously. The resultant composition of the cartilage suggests that the loss may primarily involve "resident" molecules originally present in healthy cartilage.Osteoarthritis (OA) is characterized by the destruction of joint cartilage. Previous studies have shown that matrix metalloproteinases (MMPs) play an important role in this degradation (1). MMPs are regulated by naturally occurring specific inhibitors known as tissue inhibitors of metalloproteinases (TIMPs) (2). These inhibitors (TIMP-1 and TIMP-2) and the MMPs collagenase 1 (MMP-1) and stromelysin (MMP-3) have been identified in the synovial fluid of patients with arthritis (3-6).