Disc degeneration is a chronic remodeling process that results in alterations of matrix composition and decreased cellularity. The objective of this work was to explore two important topics related to disc degeneration:​ 1.) the role o f mechanical loading in alterations of disc biology, and 2.) the potential to repair degenerated discs. The first study tested the hypothesis that dynamic mechanical forces are im portant regulators of disc cellularity and m atrix synthesis. The second study hypothesized that exogenous growth factors can stimulate regenerative remodeling in the degenerated disc in vivo. To study dynamic forces, a murine model of dynamic loading was developed that used an external loading device to cyclically compress a single disc in the tail. Dynamic loading induced differential effects that depended on frequency and stress. The results suggested a tolerance to loading above which evidence of both an anabolic response (increased proteoglycan content and matrix gene expression) and a degenerative response (cell death) were found. Finite elem ent modeling suggested that the responses m ight be due to variation of strain environment.

The effects of exogenous growth factors on degenerated discs were studied in vivo using a murine model o f compression-induced degeneration. Degenerated discs were given single or m ultipie injections of GDF-5, TGF-β, IGF-1, bFGF, or saline as control and analyzed either one week o r four weeks after treatment- In some growth factor treated discs, expansion of inner annular chondrocyte populations into the nucleus were observed. The results indicated that annular chondrocytes may be responsive to some growth factors in vivo, and that GDF-5 and TGF-β may be m itogens for annular chondrocytes.

In summary, this work provides new knowledge of the mechanisms of tissue remodeling in situ in the intervertebral disc. The results have im plications in the prevention and treatment of disc degeneration. The responses to dynamic mechanical forces suggest that loading conditions m ay be optimized to promote m aintenance of normal structure and function. The cellular response to growth factors observed in degenerated discs demonstrates the possibility of their use in new therapeutic modalities for repair.