Altered and restored function after reduced nucleus pulposus glycosaminoglycan content in the rat lumbar intervertebral disc
Intervertebral disc degeneration is a highly prevalent disorder with connections to low back pain. Among the early changes in degeneration is a reduction in glycosaminoglycan content in the nucleus pulposus of the disc. How this biochemical change alters disc health and function is not well defined, though such knowledge is needed to develop therapeutics to halt or reverse degeneration. The overall objective of this work was to model reduced nucleus glycosaminoglycan, as in early degeneration, in a rat lumbar disc to better understand the impact of this change on disc structure, mechanics, and biochemistry and on the progression of disc degeneration. To determine the impact of reduced nucleus glycosaminoglycan on disc mechanics, an in vitro model of this biochemical change was created. Nucleus glycosaminoglycan levels correlated with disc mechanics with loss leading to a state of hypermobility. Dynamic viscoelastic testing demonstrated a similar relationship at low compressive loads across a spectrum of frequencies and showed an increase in phase angle with glycosaminoglycan loss. Thus, reduced glycosaminoglycan can directly alter disc mechanics and may contribute to degeneration progression through mechanical means. Reduced glycosaminoglycan was modeled in a rat lumbar disc in an in vivo environment with temporal changes in disc properties evaluated up to 24 weeks post reduction. Initial changes in mechanics, biochemistry, and height consistent with early human degeneration were noted; however, a response more akin to regeneration than degeneration was observed as properties recovered towards control levels by 24 weeks. No association between the altered nucleus biochemistry and degeneration-like changes in cellularity or disc morphology were observed. Analysis of aggrecan fragmentation revealed an apparent decrease in catabolism in this model, which may be responsible in part for the recovery of disc properties. In summary, in vitro and in vivo models of reduced nucleus pulposus glycosaminoglycan were established and utilized to better understand the role of this change in early degeneration. It is plausible that progression occurs through mechanical means, though damage progression was not observed in vivo. Instead, the potential for anti-catabolic mediated disc recovery was demonstrated, which may prove a viable option for future therapeutic strategies.
Boxberger, John I, "Altered and restored function after reduced nucleus pulposus glycosaminoglycan content in the rat lumbar intervertebral disc" (2009). Dissertations available from ProQuest. AAI3363257.