Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes.
Cadherins are integral membrane proteins expressed in tissue-restricted patterns that mediate homophilic intercellular adhesion. During development, they orchestrate tissue morphogenesis and, in the adult, they determine tissue integrity and architecture. The synovial lining is a condensation of fibroblast-like synoviocytes (FLS) and macrophages one to three cells thick. These cells are embedded within the extracellular matrix, but the structure is neither an epithelium nor an endothelium. Previously, the basis for organization of the synovium into a tissue was unknown. Here, we cloned cadherin-11 from human rheumatoid arthritis (RA)-derived FLS. We developed L cell transfectants expressing cadherin-11, cadherin-11 fusion proteins, and anti-cadherin-11 mAb. Cadherin-11 was found to be expressed mainly in the synovial lining by immunohistologic staining of human synovium. FLS adhered to cadherin-11-Fc, and transfection of cadherin-11 conferred the formation of tissue-like sheets and lining-like structures upon fibroblasts in vitro. These findings support a key role for cadherin-11 in the specific adhesion of FLS and in synovial tissue organization and behavior in health and RA.
Valencia
Xavier
X
Dept. of Medicine, Div. of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Smith Bldg., Rm. 552, One Jimmy Fund Way, Boston, MA 02115, USA.
Higgins
Jonathan M G
JM
Kiener
Hans P
HP
Lee
David M
DM
Podrebarac
Theresa A
TA
Dascher
Christopher C
CC
Watts
Gerald F M
GF
Mizoguchi
Emiko
E
Simmons
Barry
B
Patel
Dhavalkumar D
DD
Bhan
Atul K
AK
Brenner
Michael B
MB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007739:L Cells; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015820:Cadherins; D011993:Recombinant Fusion Proteins; C086960:osteoblast cadherin