Experimental arthritis in C57black/6 normal and beige (Chediak-Higashi) mice: in vivo and in vitro observations on cartilage degradation.
Mice with the beige mutation are known to be deficient for polymorphonuclear leucocyte (PMN) elastase and cathepsin G and can therefore be used as a model for protease dependence of tissue destruction in inflammatory conditions. The in vitro and in vivo effect of PMN activation on cartilage damage in C57black/6 normal and beige mice was measured. In vitro it was found that stimulation of normal PMNs with chemotactic peptide caused degradation of articular cartilage matrix owing to an elastase dependent mechanism; PMNs of beige mice did not induce degradation of cartilage. In vivo, using zymosan induced arthritis, which is a model characterised by a PMN-rich infiltrate and exudate, no significant differences were found between the two strains with respect to (a) joint oedema formation as measured by technetium-99m uptake; (b) matrix degradation as measured quantitatively and with histology; (c) chondrocyte proteoglycan synthesis as measured by radiosulphate uptake. At day 28 after induction of arthritis, when inflammation is waning, no differences in end stage irreversible damage to joint tissues were found. The relevance of these observations to the supposed role of PMN derived neutral proteases in joint inflammation is discussed.
Schalkwijk
J
J
Department of Rheumatology, University Hospital St Radboud, University of Nijmegen, The Netherlands.
Joosten
L A
LA
van den Berg
W B
WB
van de Putte
L B
LB
D000818:Animals; D001168:Arthritis / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D010196:Pancreatic Elastase / Q000378:metabolism; D012697:Serine Endopeptidases
D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D010196:Pancreatic Elastase