Blood-induced joint damage: a human in vitro study.
OBJECTIVE
To investigate mechanisms underlying cartilage damage caused by brief exposure of cartilage to blood, such as that occurring during intraarticular bleeding.


METHODS
Human articular cartilage was cultured for 4 days in the presence of blood (components; 7.5-50% volume/volume). The synthesis of cartilage matrix, as determined by proteoglycan synthesis (incorporation of 35SO4(2-)), was measured directly after exposure and after a recovery period of 20 days, during which the cartilage was cultured in the absence of blood or blood components. The production of the cytokines interleukin-1 (IL-1) and tumor necrosis factor a (TNFalpha), which have a destructive effect on cartilage, was determined by enzyme-linked immunosorbent assay, and the viability of chondrocytes was determined by measuring lactate dehydrogenase release and with electron microscopy. The involvement of oxygen metabolites was evaluated by using N-acetylcysteine.


RESULTS
Brief exposure to blood resulted in dose-dependent inhibition of proteoglycan synthesis. The combination of mononuclear cells and red blood cells was responsible for this effect. The effect was irreversible, independent of IL-1 and TNFalpha production, and was accompanied by chondrocyte death. These effects were partially prevented by N-acetylcysteine.


CONCLUSIONS
Brief exposure of cartilage to blood, as occurs after a single episode or a limited number of bleeding episodes, results in lasting cartilage damage in vitro, in which cytotoxic oxygen metabolites play a role.
D000368:Aged; D001769:Blood; D002358:Cartilage, Articular / Q000166:cytology / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006395:Hemarthrosis / Q000150:complications / Q000473:pathology; D006801:Humans; D007592:Joint Diseases / Q000209:etiology / Q000473:pathology; D007596:Joints / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism / Q000633:toxicity; D011509:Proteoglycans / Q000096:biosynthesis