Cadherin-11 induces rheumatoid arthritis fibroblast-like synoviocytes to form lining layers in vitro.
The synovial lining of diarthrodial joints is composed of a condensed network of synoviocytes that form an intact layer via cell-to-cell contacts with significant intercellular matrix spaces. However, the molecular basis for synovial lining formation and its structural integrity has not been previously defined. In this study, using a three-dimensional fibroblast-like synoviocyte in vitro organ culture system, we provide evidence that cadherin-11 expressed in fibroblast-like synoviocytes plays a determining role in establishing the synovial lining layer. Fibroblast-like synoviocytes that were grown in three-dimensional matrices demonstrated formation of a lining structure at the interface between the matrix and the fluid phase. Treatment of fibroblast-like synoviocyte organ cultures with a cadherin-11-Fc fusion protein efficiently abrogated lining layer organization. Moreover, because E-cadherin-expressing fibroblasts failed to organize a lining layer structure at the tissue boundary, this effect appears to be a distinct characteristic of fibroblasts expressing cadherin-11. We found that cadherin-11 mediated fibroblast-like synoviocyte cell-to-cell adhesion via formation of adherens junctions that were linked to and remodeled the actin cytoskeleton. Together, these studies implicate cadherin-11 in synovial tissue and lining layer formation and provide an in vitro system to model fibroblast-like synoviocyte behavior and function in organizing the synovial tissue.
Kiener
Hans P
HP
Brigham and Women's Hospital and the Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Harvard Medical School, Boston, Massachusetts 02115, USA.
Lee
David M
DM
Agarwal
Sandeep K
SK
Brenner
Michael B
MB
D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000502:physiology*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007739:L Cells; D051379:Mice; D012155:Reticulin / Q000378:metabolism / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D046509:Tissue Culture Techniques; D014162:Transfection; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D012155:Reticulin; D016596:Vinculin; C086960:osteoblast cadherin