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Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-β induces expression of matrix metalloproteinases 3 and 10 independently of nuclear factor-κB
  1. K Warstat1,
  2. T Pap2,
  3. G Klein3,
  4. S Gay4,
  5. W K Aicher1
  1. 1
    Center for Medical Research (ZMF), Department of Orthopedic Surgery, Eberhard-Karls-University Medical School, D-72072 Tübingen, Germany
  2. 2
    Division of Molecular Medicine of Musculoskeletal Tissue, Department of Orthopedics, Münster University Hospital, D-48149 Münster, Germany
  3. 3
    Center for Medical Research (ZMF), Section for Transplantation Immunology, University of Tübingen, D-72072 Tübingen, Germany
  4. 4
    WHO Center for Experimental Rheumatology, Zürich Center for Integrative Human Physiology (ZIHP), University Hospital Zürich, CH-8090 Zürich, Switzerland
  1. Wilhelm K Aicher, ZMF, Center for Medical Research, University of Tübingen Medical School, Waldhoernle Strasse 22, D 72072 Tübingen; Aicher{at}uni-tuebingen.de

Abstract

We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-β induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription–polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-β induced significant increases in MMP-3 mRNA (12.35-fold, p<0.001) and protein (mean 62 ng/ml, sixfold, p<0.008) and in expression of MMP-10 mRNA (11.68-fold, p<0.05) and protein (54 ng/ml, 20-fold, p⩾0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor-β response. No phosphorylation of nuclear factor-κB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-β suffices to induce significant expression of MMP-3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-κB phosphorylation.

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Footnotes

  • Funding: This project was supported by DFG grants (Ai16/10 and Ai16/14) and in part by institutional funding. SG was supported by the European Community FP6 Programme. This publication reflects the authors’ views. The EC is not liable for any use that may be made of the information in the manuscript. There is no disclosure for this publication by any of the authors.

  • Competing interests: None.

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