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

Walakovits, Lori A.; Moore, Vernon L.; Bhardwaj, Nina; Gallick, Gregory S.; Lark, Michael W.

doi:10.1002/art.1780350106

Cited by 245 publications

(144 citation statements)

References 31 publications

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“…Other MMPs may contribute to the overall balance of enzymes and inhibitors; for example, the level of stromelysin in RA fluid has been reported to be 40,100 ng/ml (24), which would lead to a large predominance of enzyme over inhibitor. Consideration of the collagenase and stromelysin data together reinforces the hypothesis that an imbalance between enzyme and inhibitors is responsible for the collagenolysis that occurs in RA.…”

Section: Discussionmentioning

confidence: 99%

The measurement of collagenase, tissue inhibitor of metalloproteinases (timp), and collagenase—timp complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis

Clark

Powell

Ramsey

et al. 1993

Arthritis & Rheumatism

152

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Objective. To compare the levels of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase-TIMP complex in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). This study aims to clarify existing data from previously used enzyme or inhibitor activity assays performed following separation by gel filtration, by using a 1-step enzyme-linked immunosorbent assay (ELISA) for each component.Methods. Total collagenase, free TIMP, and collagenase-TIMP complex were measured using a newly developed, specific double-antibody sandwich ELISA.Results. Levels of both collagenase and TIMP were significantly higher in RA patients (collagenase 1,560 f 150 ng/ml [mean f SEMI, TIMP 1,610 f 130 ng/ml; n = 80) than OA patients (collagenase 420 f 90 ng/ml, TIMP 1,050 f 60 ng/ml; n = SO), with the difference being especially striking for collagenase. Sixteen RA fluids had detectable levels of collagenase-TIMP complex, compared with only 3 OA fluids.Conckusion. The level of total collagenase in SF is greater in RA than OA, while levels of free TIMP show more overlap between the 2 diseases; this may simply ~~ --

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Section: Discussionmentioning

confidence: 99%

The measurement of collagenase, tissue inhibitor of metalloproteinases (timp), and collagenase—timp complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis

Clark

Powell

Ramsey

et al. 1993

Arthritis & Rheumatism

152

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“…Results were expressed as equivalents of intact adult human knee joint cartilage proteoglycan per milliliter SF. Concentrations of MMPs 1 and 3 and tissue inhibitor of metalloproteinases 1 (TIMP-1) in SF were determined by sandwich immunoassays, as previously described (15,46). These assays detect the pro forms of the proteases, the intact active forms, and the enzymes complexed to TIMP-1 (46).…”

Section: Methodsmentioning

confidence: 99%

“…Concentrations of MMPs 1 and 3 and tissue inhibitor of metalloproteinases 1 (TIMP-1) in SF were determined by sandwich immunoassays, as previously described (15,46). These assays detect the pro forms of the proteases, the intact active forms, and the enzymes complexed to TIMP-1 (46). Results were expressed as nM equivalents of the pro forms of the enzymes and inhibitor per milliliter of SF.…”

Section: Methodsmentioning

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

Arthritis & Rheumatism

234

165

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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

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“…than 5% of total MMP), net enzyme activity is more appropriate than total amounts of (pro)MMPs plus MMP-TIMP complexes as frequently determined by immunoassay [4][5][6][7]. Activity assays from MMPs comprise methods based on physiological substrates (e.g.…”

Section: Introductionmentioning

confidence: 99%

Convenient fluorometric assay for matrix metalloproteinase activity and its application in biological media

Beekman¹,

Drijfhout

Bloemhoff

et al. 1996

FEBS Letters

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Matrix metalloproteinases (MMPs) are involved in physiological tissue remodeling and pathological conditions like tumour metastasis and joint destruction. Until now, no convenient and sensitive MMP-activity assay in crude media like synodal fluid has been available. Therefore, the highly soluble fluorogenic substrate TNO211 (Dabcyl-Gaba-Pro-Gin-Gly-LeuGIu(EDANS)-AIa-Lys-NH2), containing the MMP cleavable Gly-Leu bond and EDANS/Dabcyl as fluorophore/quencer combination, was synthesized and characterized as an MMP specific substrate. We show that the fluorogenic assay using ] NO211 is sensitive and can detect MMP activity in culture medium from endothelial cells and untreated synovial fluid (SF) from RA and OA patients, and control subjects. MMP activity in SF significantly increased in the order C < OA < RA, thus the frequent use of OA samples as control in studies on RA is debatable.A ey words: Matrix metalloproteinase; Synovial fluid; I luorescence quenching

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

Cited by 245 publications

References 31 publications

The measurement of collagenase, tissue inhibitor of metalloproteinases (timp), and collagenase—timp complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis

The measurement of collagenase, tissue inhibitor of metalloproteinases (timp), and collagenase—timp complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis

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

Convenient fluorometric assay for matrix metalloproteinase activity and its application in biological media

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