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Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. I: Collagen synthesis

  • Inflammation and Immunomodulation
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Abstract

Cultures of human rheumatoid synovial cells and rabbit articular chondrocytes were exposed to various concentrations of Etodolac (from 0.01 to 10 μg/ml) in presence or absence of 500 pg/ml (5 U/ml) human recombinant Interleukin-1β (IL-1β). Incubation of chondrocytes with Etodolac for 24 h did not alter collagen biosynthesis. In contrast, 1 μg/ml Etodolac caused a 20% increase of collagen production in synoviocytes. Addition of Etodolac in combination with IL-1 could partially suppress the inhibitory effect exerted by the cytokine on both cell types. Four-day exposure of chondrocytes to 0.1 and 1 μg/ml Etodolac led to an increased accumulation of collagen in the cell layer compartment. However, this treatment could not prevent the inhibitory effect of IL-1 on this collagen fraction. Treatment of synoviocytes for eight days with the same concentrations of Etodolac did not modify their collagen production but suppressed totally the inhibitory effect of IL-1. These data show that Etodolac is able to augment chondrocyte metabolism during a long term treatment. Moreover, under certain conditions, this drug can reduce or even suppress the IL-1-induced inhibition of collagen biosynthesis, a process that may take a part in the connective tissue alterations associated with osteoarticular diseases such as rheumatoid arthritis and osteoarthritis.

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Abbreviations

β-APN:

β-aminopropionitrile

C:

collagen

DMEM:

Dulbecco's modification of Eagle's essential medium

FCS:

fetal calf serum

IL-1:

Interleukin-1

NCP:

non-collagenous protein

NSAID:

nonsteroidal antiinflammatory drug

PG:

prostaglandin

SF:

synovial fluid

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Authors and Affiliations

  1. Laboratoire de Biochimie du Tissue Conjonctif, C.H.U. Côte de Nacre, 14033, Caen Cédex, France

    A. Mauviel, F. Redini, G. Loyau & J. -P. Pujol

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  1. A. Mauviel
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  2. F. Redini
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  3. G. Loyau
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  4. J. -P. Pujol
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Additional information

We thank R. Béliard (Laboratoire d'Anatomie Pathlogique, C.H.U. Caen) for expert technical assistance and Dr. D. Lando (Roussel Uclaf, France) for kindly providing human recombinant Interleukin-1β. This work was financially supported by Wyeth France.

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Mauviel, A., Redini, F., Loyau, G. et al. Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. I: Collagen synthesis. Agents and Actions 31, 345–352 (1990). https://doi.org/10.1007/BF01997630

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