Induction of a rapid progessive cartilage destruction in SCID mice by intraarticular application of a murine fibroblast like cell line

Background

In pathogenesis of rheumatoid arthritis, fibroblasts are considered to be a crucial cell population for disease progression as well as joint destruction. Following intraarticular injection into SCID mice, isolated human rheumatoid synovial fibroblasts have been shown to induce a destructive arthritis (hu/mu SCID arthritis). Although exclusively human synovial fibroblasts were able to induce this arthritis, cartilage destruction was caused by murine fibroblast like cells in this model. Therefore, we have isolated a murine destructive fibroblastoid cell line and established a cartilage destruction model.

Material and methods

LS48 cell line was examined for morphological, ultrastructural, immunological, and functional parameters. Furthermore, cartilage destruction was induced by intraarticular application of LS48 cells into SCID mouse knee joints. Mice were monitored for joint swelling, serological parameters and by radiological methods. Finally, immunohistochemistry and histology were used to characterize morphology of cartilage destruction.

Results

LS48 was shown to present characteristics of a fibroblast-like cell. Secretion of interleukin-6 and tumor necrosis factor-alpha revealed similarities to human invasive rheumatoid synovial membrane fibroblasts. Installation of 5 × 10⁵ cells into SCID mouse knee joints caused a rapid progressive process causing cartilage destruction within 10 days. Morphology revealed infiltration of fibroblast like cells into the cartilage.

Conclusions

Induction of cartilage destruction by intraarticular application of these murine fibroblast like cells is a rapid and highly reproducible model for investigation of cartilage destruction in arthritic joints. This provides an excellent possibility to investigate relevant processes and new therapeutic strategies for rheumatoid arthritis in an easy-to-handle animal model.