Increased release of matrix components from articular cartilage in experimental canine osteoarthritis

Ratcliffe, Anthony; Billingham, M. E. J.; Saed‐Nejad, Fatemeh; Muir, Helen; Hardingham, Timothy E.

doi:10.1002/jor.1100100307

Cited by 66 publications

(51 citation statements)

References 57 publications

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“…The findings of the present study are similar to those previously described in this model of experimental OA (8,20,21), in which the turnover of * Osteoarthritis (OA) was induced in the right stifle joint of adult female animals as described in Materials and Methods. The left stifle joint served as a control.…”

Section: Resultssupporting

confidence: 90%

Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis

Venn

Nietfeld

Duits

et al. 1993

Arthritis & Rheumatism

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Objective. To measure levels of cytokines, proteases, and glycosaminoglycans (GAG) in synovial fluid (SF) From the knees of animals with experimental osteoarthritis (OA) and from their contralateral (control) knees, and to compare and correlate these values with each other as well as with measures of proteoglycan synthesis in the corresponding articular cartilage. This study will help to identify cytokines of potential importance in the early stages of the development of OA.Methods. OA was induced in 12 mature animals by sectioning the anterior cruciate ligament. After 3 months, SF From the operated and contralateral (control) knee joints was assayed for interleukind (IL-6), tumor necrosis Factor (TNF), IL-1, latent metalloproteinase, and sulfated GAG. Proteoglycan synthesis in the corresponding articular cartilage was also measured.Results. IL-6 levels in SF from the operated joint compared with the control joint were significantly ele- Submitted for publication July 9, 1992; accepted in revised form January 6, 1993. vated in 11 of 12 animals. TNF levels were also elevated in 10 of 11 SF samples from operated joints, but to a lesser extent than those of IL-6. IL-1 and IL-1 inhibitors were undetectable in either the operated or control joint SF. The GAG concentration was elevated in SF from experimental OA joints. This elevation correlated with that of TNF, but not IL-6. There was no significant difference in the concentration of APMA-activatable metalloproteinase. The rate of proteoglycan synthesis was higher in the cartilage from the operated joint in 8 of 12 animals, and the mean rate of synthesis was significantly higher than in the control joint. There was a positive correlation between this increase in cartilage proteoglycan synthesis (operated versus control) and the increase in SF IL-6, but there was no correlation with the levels of TNF or GAG.Conclusion. This is the first study of SF levels of cytokines in early experimental OA. Our results show surprisingly high levels of IL-6 in operated joints, where the cytokine could act directly on the chondrocytes, and thus play a role in mediating their responses to cartilage injury.

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Section: Resultssupporting

confidence: 90%

Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis

Venn

Nietfeld

Duits

et al. 1993

Arthritis & Rheumatism

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“…Both disorders involve accelerated breakdown and loss of proteoglycan (3,6,9,20,39), but they are regarded as fundamentally different because in disuse the cartilage can recover after remobilization (19,30,41), whereas in osteoarthritis the degeneration appears to be irreversible ( 5 ) . Previous studies have indicated that the analysis of synovial fluid for levels of cartilage matrix components (for example, keratan sulfate epitope, sulfated glycosaminoglycan, and link protein [39], as in this study) can be used as indicators, or markers, of catabolic activity in the tissue (15,36,38,39,52). The results of this study indicate that the catabolic events affecting proteoglycans in the articular cartilage of joints with osteoarthritis and disuse atrophy are different.…”

Section: Discussionmentioning

confidence: 97%

“…In a previous study. we showed that in early experimental osteoarthritis there is an increased release of proteoglycan aggregate components from the articular cartilage (39). Two of these components.…”

Section: Synoviai Fluid Markers I N Experimental Osteoarthritjs a N mentioning

confidence: 98%

Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse

Ratcliffe

Beauvais

Saed‐Nejad

1994

Journal Orthopaedic Research

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The levels of proteoglycan aggregate components (link protein, keratan sulfate epitope, and total sulfated glycosaminoglycan) were determined in the synovial fluid lavages of dogs with experimental osteoarthritis or disuse atrophy. A model of experimental osteoarthritis was created by transection of the anterior cruciate ligament of the right knee; studies were carried out 6 and 12 weeks after surgery. Joint disuse was studied at 4 and 8 weeks after initiation of the disuse. Recovery after disuse also was studied in joints that had 3 weeks of remobilization after 4 or 8 weeks of disuse. Synovial fluid lavages from the right knee joints of untreated animals were used as controls. The concentrations of keratan sulfate epitope, sulfated glycosaminoglycan, and link protein in the synovial fluid lavages at 6 and 12 weeks after transection of the anterior cruciate were elevated compared with the control values. Similar analysis of the fluid after disuse showed that the levels of keratan sulfate epitope and sulfated glycosaminoglycan were increased compared with the control levels and the levels after transection. However, the concentration of link protein in the fluid after disuse was not significantly different from the control level. The levels of keratan sulfate epitope and sulfated glycosaminoglycan in the synovial fluid lavages after disuse with recovery were high, but the levels of link protein remained low. The results indicate that the catabolism of proteoglycan aggregates in articular cartilage during early osteoarthritis and disuse is different. The determination of keratan sulfate epitope in synovial fluid lavages appears to provide a relatively general indication of proteoglycan catabolism, whereas increased levels of link protein may be more indicative of cartilage degeneration.

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“…Intra-articular injection of IL-1 concentrated in the middle and upper cell layers of the cartilaginous matrix in rheumatoid and osteoarthritis [6,9] and it interferes with normal cartilage metabolism [11,13]. TNF and IL-1 are two different cytokines with nearly the same biological action.…”

Section: Discussionmentioning

confidence: 99%

Measurement of the bioactivity of interleukin and tumour necrosis factor in synovial fluid of Kashin-Beck disease

Wang

Tong

Gong

et al. 2001

International Orthopaedics (SICOT)

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We studied the bioactivity of interleukin-1 (IL-1) and tumour necrosis factor (TNF) in the synovial fluid of 12 patients with Kashin-Beck disease (KBD), 8 patients with osteoarthritis (OA) and 8 normal controls. C57 female mouse T cell proliferation method was used to test the bioactivity of IL-1, and lethality method with L929 cells to test the bioactivity of TNF. The bioactivities of IL-1 and TNF in the synovial fluid from patients with KBD were higher than those in the synovial fluid of osteoarthritis and normal controls, indicating the participation of IL-1 and TNF in the pathogenesis of KBD.Résumé Nous avons étudié la bioactivité de l'interleukin-1 (IL-1) et du facteur de nécrose tumorale (TNF) dans le liquide synovial de 12 patients atteints de la maladie de Kashin-Beck (KBD), 8 patients d'arthrose et 8 sujets té-moins. La bioactivité de IL-1 est évaluée par la méthode de prolifération des cellules T de souris femelles C57 et le TNF par la mortalité des cellules L929. L'activité d'IL-1 et de TNF dans le liquide synovial des patients atteints de KBD est plus élevée que pour l'arthrose et les sujets normaux, révélant la participation d'IL-1 et de TNF dans la pathogenèse de la maladie de Kashin-Beck.

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Increased release of matrix components from articular cartilage in experimental canine osteoarthritis

Cited by 66 publications

References 57 publications

Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis

Elevated synovial fluid levels of interleukin‐6 and tumor necrosis factor associated with early experimental canine osteoarthritis

Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse

Measurement of the bioactivity of interleukin and tumour necrosis factor in synovial fluid of Kashin-Beck disease

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