Development of in vitro model systems for destructive joint diseases: novel strategies for establishing inflammatory pannus.
OBJECTIVE
To establish a novel 3-dimensional (3-D) in vitro model for the investigation of destructive processes in rheumatoid arthritis (RA).


METHODS
Two distinct culture systems were developed, consisting of RA synovial membrane and articular cartilage explants or interactive RA synovial cell/chondrocyte cultures embedded in 3-D fibrin matrices. The expression of proteolytic enzymes, chondrocyte matrix architecture, and matrix degradation parameters was analyzed by immunohistochemistry.


RESULTS
Of 28 RA explant cultures, 16 displayed an invasion of synovial tissue into the cartilage explants, compared with 1 of 8 osteoarthritis explants. The expression of collagenase and vascular cell adhesion molecule 1 could be demonstrated at the cartilage-pannus junction. Of 20 interactive cell cultures, 18 revealed invasive behavior and remained vital for extended periods of time.


CONCLUSIONS
The models presented allow us to study distinct aspects of destructive joint diseases under in vitro conditions that resemble human pathology. Moreover, our model is able to supplement animal experiments in basic research and drug testing.
Schultz
O
O
Humboldt University, Berlin, Germany.
Keyszer
G
G
Zacher
J
J
Sittinger
M
M
Burmester
G R
GR
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000503:physiopathology; D002478:Cells, Cultured; D017364:Collagenases / Q000032:analysis; D046508:Culture Techniques; D005347:Fibroblasts / Q000737:chemistry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000276:immunology; D020781:Matrix Metalloproteinase 1; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013583:Synovial Membrane / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017364:Collagenases; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D020781:Matrix Metalloproteinase 1; D018809:Proliferating Cell Nuclear Antigen; D019010:Vascular Cell Adhesion Molecule-1; C067980:CD68 antigen, human; D000097382:CD68 Molecule