Development of in vitro model systems for destructive joint diseases. Novel strategies for establishing inflammatory pannus

Abstract

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. Conclusion. 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.