The Extent and Distribution of Cell Death and Matrix Damage in Impacted Chondral Explants Varies with the Presence of Underlying Bone

Abstract

Excessive mechanical loading can lead to matrix damage and chondrocyte death in articular cartilage. Previous studies on chondral and osteochondral explants have not clearly distinguished to what extent the degree and the distribution of cell death are dependent on the presence of an underlying layer of bone. The current study hypothesized that the presence of underlying bone would decrease the amount of matrix damage and cell death. Chondral and osteochondral explants were loaded to 30 MPa at a high rate of loading (approximately 600 MPa/s) or at a low rate of loading (30 MPa/s). After 24 hours in culture, matrix damage was assessed by the total length and average depth of surface fissures. The explants were also sectioned and stained for cell viability in the various layers of the cartilage. More matrix damage was documented in chondral than osteochondral explants for each rate of loading experiment. The total amount of cell death was also less in osteochondral explants than chondral explants. The presence of underlying bone significantly reduced the extent of cell death in all zones in low rate of loading tests. The percentage of cell death was also reduced in the intermediate zone and deep zones of the explant by the presence of the underlying bone for a high rate of loading. This study indicated that the presence of underlying bone significantly limited the degree of matrix damage and cell death, and also affected the distribution of dead cells through the explant thickness. These data may have relevance to the applicability of experimental data from chondral explants to the in situ condition.

Effect of Compressive Strain on Cell Viability in Statically Loaded Articular Cartilage

“…Finally, several in vivo animal studies have confirmed that trauma-induced chondrocyte death is followed by progressive degenerative joint changes (Radin et al 1973;Ewers et al 2001;Krueger et al 2003;. Thus, preservation of cell viability in articular cartilage after mechanical damage is important for matrix integrity and tissue healing, and ultimately in the prevention of OA.…”

Basic fibroblast growth factor mediates transduction of mechanical signals when articular cartilage is loaded

“…Other investigators have failed to demonstrate such changes in MMP expression, but have reported a reduction in type II collagen mRNA upon cyclical loading (13). Cell death, by apoptosis and necrosis, is increased in cartilage explants subjected to high static loads, especially in the superficial zone (14)(15)(16), although loading the tissue still attached to bone causes less cell death (17).…”

The effect of finite compressive strain on chondrocyte viability in statically loaded bovine articular cartilage

“…Recent studies have reported that static and cyclic compressive loading of varying magnitudes, as well as blunt impacts, result in increased cell death in articular cartilage (Chen et al 1999(Chen et al , 2003Torzilli et al 1999;Ewers et al 2001;Quinn et al 2001;Lucchinetti et al 2002;Krueger et al 2003). Examination of the distribution of cell death has been shown to be preferentially concentrated in the superficial tangential zone (STZ) after cyclic loading at moderate magnitudes (peak stress of 1 MPa) (Lucchinetti et al 2002;Chen et al 2003).…”

“…e Schematic of samples tested in the microscopy device shown in d the relationship between the depth-dependent strain and cell death on the same tissue type or under the same loading configuration. Moreover, injury studies have generally examined the behavior of cell death under impact and/or cyclic loading with load control that results in large compressive strain magnitude, typically up to 50-60% strain (Ewers et al 2001;Flachsmann et al 2001;Krueger et al 2003), whereas the literature studies on the depth-dependent mechanical properties of cartilage have generally been tested under a smaller strain range, typically 20-30% strain.…”