A novel model of fibroblast-mediated cartilage destruction.
In rheumatoid arthritis (RA), fibroblasts have been shown to be crucial for disease progression as well as joint destruction. In the model of human/murine SCID arthritis, synovial explants as well as fibroblasts from human rheumatoid synovial membrane induce destructive arthritis in immunodeficient mice. Hereby, the underlying cartilage destruction is accomplished by murine fibroblasts. Therefore, murine destructive fibroblasts represent a promising tool to investigate destruction of articular cartilage and bone. In this context, a novel destructive murine fibroblast line (LS48) was examined for morphological, ultrastructural, immunological and functional cellular parameters. These cells were injected into knees of SCID mice. Subsequently, the animals were monitored for joint swelling and serological parameters of arthritis by radiological methods. Finally, cartilage destruction was assessed morphologically. Cultured LS48 cells exhibit characteristic features that resemble those of activated synovial fibroblasts in human RA. Expression levels of inducible nitric oxide synthase, interleukin-6, tumour necrosis factor-alpha and matrix metalloproteinases were comparable to those detected in invasive human fibroblasts. The instillation of 5 x 10(5) LS48 cells into the knee joints of SCID mice initiated a rapid progressive process, that caused cartilage destruction within 10 days, and morphological examinations revealed that articular cartilage was infiltrated by the fibroblasts injected previously. In summary, the intra-articular application of LS48 cells represents a rapid and highly reproducible model to investigate the initiation and progression of cartilage destruction in connection with RA therapy and represents an easy-to-handle animal model.
Sack
U
U
Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig, Leipzig, Germany. ulrich.sack@medizin.uni-leipzig.de
Hirth
A
A
Funke
B
B
Wiedemeyer
K
K
Lange
F
F
Tröltzsch
M
M
Tannapfel
A
A
Gebhardt
R
R
Emmrich
F
F
Lehmann
J
J
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D002356:Cartilage / Q000473:pathology*; D002460:Cell Line; D018920:Coculture Techniques; D017364:Collagenases / Q000235:genetics; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology
D015850:Interleukin-6; D012333:RNA, Messenger; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9