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Arthritis Research & Therapy

Open Access

The synovial cadherin (cadherin-11) mediates tissue formation and promotes invasion of fibroblast-like synoviocytes

  • H Kiener1,
  • J Higgins1,
  • X Valencia1 and
  • M Brenner1
Arthritis Res Ther20035(Suppl 3):148

https://doi.org/10.1186/ar949

Published: 12 September 2003

Keywords

SynovitisInvasive CapacityControl Empty VectorSynovial LiningMatrigel Invasion Assay

Cadherins are integral membrane homophilic adhesion proteins that mediate adhesion between cells of the same type within a tissue. Cadherins mediate tissue morphogenesis during development and maintenance of tissue architecture in adults. We recently found that cadherin-11 is expressed in human fibroblast-like synoviocytes. We demonstrate that the expression of the synovial cadherin promotes cell invasion and confers on cells the ability to become organized into synovial lining-like architecture in vitro.

We generated cadherin-11-expressing fibroblast L-cell clones and empty vector transfected L-cell controls. Phase-contrast microscopy analysis demonstrated that cadherin-11-transfected L-cells form extensive and intimate contacts along their surfaces, and condense together at higher cell density to form a continuous sheet of cells in vitro. In contrast, L-cells transfected with control empty vector are loosely organized and do not form a tissue-like structure. We have established an in vitro model for synovial lining formation. Interestingly, at the edge of fibronectin-coated culture areas, the cadherin-11-expressing L-cells piled up and formed a continuous lining layer-like architecture after 2 days in culture, whereas the control L-cells failed to form this lining morphology.

Matrigel invasion assays revealed a twofold to threefold increased invasive capacity of the cadherin-11-transfected L-cells when compared with L-cells transfected with control vector. To determine the molecular mechanisms of cadherin-11-dependent cell invasion, we generated cadherin-11 constructs of the cytoplasmic tail that delete domains implicated in binding critical intracellular molecules that control cadherin function. Strikingly, deletion of the juxtamembrane domain, known to bind p120-catenin, profoundly altered the invasive capacity of these cells.

These in vitro studies suggest a role for cadherin-11 in tissue and lining layer formation in the synovium and the invasive nature of fibroblast-like synoviocytes in chronic synovitis and in rheumatoid arthritis.

Authors’ Affiliations

(1)
Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, USA

Copyright

© The Author(s) 2003

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