An in vivo model of reduced nucleus pulposus glycosaminoglycan content in the rat lumbar intervertebral disc

Study Design. An in vivo model resembling early stage disc degeneration in the rat lumbar spine. Objective. Simulate the reduced glycosaminoglycan content and altered mechanics observed in intervertebral disc degeneration using a controlled injection of chondroitinase ABC (ChABC). Summary of Background Data. Nucleus glycosaminoglycan reduction occurs early during disc degeneration; however, mechanisms through which degeneration progresses from this state are unknown. Animal models simulating this condition are essential for understanding disease progression and for development of therapies aimed at early intervention. Methods. ChABC was injected into the nucleus pulposus, and discs were evaluated via micro-CT, mechanical testing, biochemical assays, and histology 4 and 12 weeks after injection. Results. At 4 weeks, reductions in nucleus glycosaminoglycan level by 43%, average height by 12%, neutral zone modulus by 40%, and increases in range of motion by 40%, and creep strain by 25% were found. Neutral zone modulus and range of motion were correlated with nucleus glycosaminoglycan. At 12 weeks, recovery of some mechanical function was detected as range of motion and creep returned to control levels; however, this was not attributed to glycosaminoglycan restoration, because mechanics were no longer correlated with glycosaminoglycan. Conclusion. An in vivo model simulating physiologic levels of glycosaminoglycan loss was created to aid in understanding the relationships between altered biochemistry, altered mechanics, and altered cellular function in degeneration.