Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis

A bovine cartilage explant system was used to evaluate the effects of injur ious compression on chondrocyte apoptosis and matrix biochemical and biomec hanical properties within intact cartilage. Disks of newborn bovine articul ar cartilage were compressed in vitro to various peak stress levels and cho ndrocyte apoptotic cell death, tissue biomechanical properties, tissue swel ling, glycosaminoglycan loss, and nitrite levels were quantified. Chondrocy te apoptosis occurred at peak stresses as low as 4.5 MPa and increased with peak stress in a dose-dependent manner. This increase in apoptosis was max imal by 24 h after the termination of the loading protocol. At high peak st resses (>20 MPa), greater than 50%, of cells apoptosed. When measured in un iaxial confined compression, the equilibrium and dynamic stiffness of expla nts decreased with the severity of injurious load, although this trend was not significant until 24-MPa peak stress, In contrast, the equilibrium and dynamic stiffness measured in radially unconfined compression decreased sig nificantly after injurious stresses of 12 and 7 MPa, respectively. Together , these results suggested that injurious compression caused a degradation o f the collagen fibril network in the 7- to 12-MPa range. Consistent with th is hypothesis, injurious compression caused a dose-dependent increase in ti ssue swelling, significant by 13-MPa peak stress. Glycosaminoglycans were a lso released from the cartilage in a dose-dependent manner, significant by 6- to 13-MPa peak stress. Nitrite levels were significantly increased above controls at 20-MPa peak stress. Together, these data suggest that injuriou s compression can stimulate cell death as well as a range of biomechanical and biochemical alterations to the matrix and, possibly, chondrocyte nitric oxide expression. Interestingly, chondrocyte programmed cell death appears to take place at stresses lower than those required to stimulate cartilage matrix degradation and biomechanical changes. While chondrocyte apoptosis may therefore be one of the earliest responses to tissue injury, it is curr ently unclear whether this initial cellular response subsequently drives ca rtilage matrix degradation and changes in the biomechanical properties of t he tissue. (C) 2000 Academic Press.