Rheumatoid arthritis synovial fibroblast and U937 macrophage/monocyte cell line interaction in cartilage degradation.
OBJECTIVE
To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation.


METHODS
An in vitro model of human cartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radiolabeled cartilage disc. Cartilage destruction was measured by the percentage of radiolabel release.


RESULTS
Fibroblasts, obtained from either rheumatoid arthritis (RA) or osteoarthritis synovial tissue, could mediate cartilage degradation if cocultured with the U937 macrophage cell line. Skin and RA bone marrow fibroblasts had no degradative effect on cartilage. Fibroblast-macrophage contact was not required for cartilage degradation. Cartilage degradation by synovial fibroblasts was inhibited by antibodies to tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6. Cartilage degradation was almost completely abrogated by a combination of antibodies to TNF alpha and IL-1 beta. Contact between fibroblasts and cartilage was shown to be essential. Antibodies to CD44, but not to intercellular adhesion molecule 1, markedly inhibited cartilage degradation.


CONCLUSIONS
TNF alpha, IL-1 beta, and IL-6 were involved in the activation of synovial fibroblasts to cause cartilage degradation. Cartilage degradation occurred only when fibroblasts were in contact with cartilage. CD44 was demonstrated to be involved in the fibroblast-cartilage interaction.
Scott
B B
BB
Wellesley Hospital Research Institute, Toronto, Ontario, Canada.
Weisbrot
L M
LM
Greenwood
J D
JD
Bogoch
E R
ER
Paige
C J
CJ
Keystone
E C
EC
D000906:Antibodies / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002358:Cartilage, Articular / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000166:cytology; D013583:Synovial Membrane / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000906:Antibodies; D018960:Hyaluronan Receptors; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha