TOPOGRAPHICAL VARIATION IN THE CATABOLISM OF AGGRECAN IN AN OVINE ANNULAR LESION MODEL OF EXPERIMENTAL DISC DEGENERATION

An established model of experimental disc degeneration (Osti et al., S pine 15:762, 1990; Melrose et al., J Orthop Res 10:665, 1992) was used in this study. Four 2-year-old sheep received anterolateral incisions (4 x 10 mm) in the outer one-third of the annulus fibrosus of their L 2-L3 and L4-L5 discs (lesion group). The annulus was not incised in an other four sham-operated animals. After 6 months the sheep were killed , lumbar discs were dissected into lateral halves of the annulus fibro sus and the nucleus pulposus. Cells were isolated from disc tissues en zymatically and were grown in alginate bead culture to examine the pro teoglycan metabolism of cells from lesion and control zones. The media of lesion zone cultures contained relatively high levels (compared wi th sham cultures) of catabolic fragments of the large, high-buoyant-de nsity proteoglycans as demonstrated by Western blotting using monoclon al antibodies (5-D-4, 3-B-3, 1-C-6) and biotinylated hyaluronan and al so by gel chromatography. Furthermore, cells from the vicinity of the lesion site also synthesized significantly lower levels (compared with sham cultures) of aggrecan that was retained within the alginate bead s. Collectively, these data indicated that focal depletion of large, h igh-buoyant-density proteoglycans was evident within lesion sites in t his model of experimental disc degeneration. The introduction of an an nular lesion therefore significantly affected the proteoglycan metabol ism of endogenous disc cell populations. The unique hydrodynamic and v iscoelastic properties of the intervertebral disc are dependent to a l arge degree on the tissue levels of aggrecan. The focal depletion of a ggrecan by annular lesions therefore may represent an important predis posing factor to the subsequent degeneration of these intervertebral d iscs.