Cadherin-11 in Synovial Lining Formation and Pathology in Arthritis

Lee, David M.; Kiener, Hans P.; Agarwal, Sandeep K.; Noss, Erika H.; Watts, Gerald F.; Chisaka, Osamu; Takeichi, Masatoshi; Brenner, Michael B.

doi:10.1126/science.1137306

Cited by 356 publications

(401 citation statements)

References 26 publications

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“…However, a faint perinuclear granular pattern of cadherin 11 expression was observed. This localization of the mutant cadherin 11, which lacks the fifth subdomain of the extracellular region and most of the transmembrane region, is consistent with the findings of previous studies demonstrating that the mutant cadherin 11 remains intracellular in other cellular lineages, including osteoblasts and FLS (6,17).…”

Section: Resultssupporting

confidence: 91%

“…Cadherin 11 has recently been identified on human and murine FLS and has been proposed to be a key mediator of synovial lining architecture and synovial inflammation (4)(5)(6). In the present study, we demonstrated that in addition to cadherin 11, FLS express a second mesenchymal cadherin, N-cadherin, but do not express the epithelial cadherin, E-cadherin.…”

Section: Discussionsupporting

confidence: 59%

“…Monoclonal antibodies specific for mouse cadherin 11 (15F7, 23C6) were generated and purified as previously described (6). Monoclonal antibodies against mouse proteins used in immunofluorescence (IF) and biochemical experiments were IgG isotype control antibody (MOPC-31C; Sigma, St. Louis, MO), anti-GAPDH (AB9484; Abcam, Cambridge, MA), anti-N-cadherin (3B9; Zymed, South San Francisco, CA), anti-cadherin 11 (5B2H5; Zymed), anti-Ecadherin (ECCD-2; Zymed), and anti-␤-catenin (clone 14; BD Biosciences PharMingen, San Jose, CA).…”

Section: Methodsmentioning

confidence: 99%

“…The molecular basis of the intercellular contacts between FLS was unclear until the recent identification of cadherin 11 expression on human FLS (4). Human studies in vitro and murine studies in vivo have now established a critical role of cadherin 11 in the development and architecture of the synovium (5,6). These studies demonstrated that mice deficient in cadherin 11 have a hypoplastic synovial lining and, upon challenge in the K/BxN serum transfer model, the inflammatory response is attenuated and cartilage destruction is reduced (6).…”

mentioning

confidence: 99%

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Coexpression of two mesenchymal cadherins, cadherin 11 and N‐cadherin, on murine fibroblast‐like synoviocytes

Agarwal

Lee

Kiener

et al. 2008

Arthritis & Rheumatism

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Objective. Cadherin 11 has recently been identified on fibroblast-like synoviocytes (FLS), and studies in mice have demonstrated its importance in synovial lining architecture and inflammation. However, many tissues express more than 1 cadherin. Given the newly appreciated functional significance of cadherins in the synovium, this study was undertaken to determine whether mouse FLS express other cadherins in addition to cadherin 11.Methods. The characterization of cadherin expression was determined in FLS derived from wild-type and cadherin 11-null mice using immunofluorescence (IF), biochemical, and immunohistologic techniques.Results. Cadherin 11 expression was observed at points of cell-cell contact in cultured wild-type mouse FLS. However, despite the lack of cell surface cadherin 11, cadherin 11-null mouse FLS cells still formed intimate cell-cell contacts that contained ␤-catenin. Immunoprecipitation of cell surface biotinylated FLS with anti-␤-catenin antibody demonstrated the presence of 2 cell surface catenin-associated proteins in FLS from wild-type mice and 1 in FLS sample from cadherin 11-null mice. Using biochemical approaches and reverse transcriptase-polymerase chain reaction, these proteins were determined to be N-cadherin and cadherin 11. Expression of both N-cadherin and cadherin 11 in the synovial lining was demonstrated by immunohistochemical analysis of mouse synovium. IF analyses demonstrated colocalization of N-cadherin and cadherin 11 to the same points of cell-cell contact. However, the inability to coimmunoprecipitate both cadherins using either anti-N-cadherin or anti-cadherin 11 antibodies suggests that these cadherins are not contained within the same molecular complexes.Conclusion. These findings demonstrate that FLS express both N-cadherin and cadherin 11, and suggest that these cadherins are not contained within the same molecular complex. Given their importance in modulating cellular behavior, understanding how these cadherins regulate FLS behavior individually and in concert will be critical to understanding synovial architecture and inflammation.

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Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Coexpression of two mesenchymal cadherins, cadherin 11 and N‐cadherin, on murine fibroblast‐like synoviocytes

Agarwal

Lee

Kiener

et al. 2008

Arthritis & Rheumatism

Self Cite

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“…T cells reside in the sublining and are therefore distal from FLS in the synovial lining. However, cadherin 11-positive cells are also found in the sublining layer in inflamed synovium and likely represent FLS migrating to the synovial lining (32). In addition, T cells may secrete soluble mediators that up-regulate the FKN-CX 3 CR1 pathway in synovial lining cells.…”

Section: Discussionmentioning

confidence: 99%