1998 Volvo Award winner in biomechanical studies - Compression-induced degeneration of the intervertebral disc: An in vivo mouse model and finite-element study

Study Design. All in vivo study of the biologic and biomechanical consequen ces of static compressive loading on the mouse tail intervertebral disc. Objectives. To determine whether static compression in vivo alters the biol ogic activity of the disc and leads to diminished biomechanical performance . Summary of Background Data. Static compressive stress that exceeds the disc 's swelling pressure is known to change hydration and the intradiscal stres s distribution. Alterations in hydration and stress have been associated wi th changes in disc cell activity in vitro and in other collagenous tissues in vivo. Methods. Mouse tail discs were loaded in vivo with an external com pression device. After 1 week at one of three different stress levels, the discs were analyzed for their biomechanical performance, morphology, cell a ctivity, and cell viability. A second group of mice were allowed to recuper ate for 1 month after the 1-week loading protocol to assess the disc's abil ity to recover. As an aid to interpreting the histologic and biologic data, finite-element analysis was used to predict region-specific changes in tis sue stress caused by the static loading regimen. Results. With increasing compressive stress, the inner and middle anulus be came progressively more disorganized, and the percentage of cells undergoin g apoptosis increased. The expression of Type II collagen was suppressed at all levels of stress, whereas the expression of aggrecan decreased at the highest stress levels in apparent proportion to the decreased nuclear cellu larity. Compression for 1 week did not affect the disc bending stiffness or strength but did increase the neutral zone by 33%. As suggested by the fin ite-element model, during sustained compression, tension is maintained in t he outer anulus and lost in the inner and middle regions where the hydrosta tic stress was predicted to increased nearly 10-fold. Discs loaded at the l owest stress recovered anular architecture but not cellularity after 1 mont h of recuperation. Discs loaded at the highest stress did not recover anula r architecture. displaying islands of cartilage cells in the middle anulus at sites previously populated by fibroblasts. Conclusions. The results of the current project demonstrate that static com pressive loading initiates a number of harmful responses in a dose-dependen t way: disorganization of the anulus fibrosus; an increase in apoptosis and associated loss of cellularity; and down regulation of collagen II and agg recan gene expression. The finite element model used in this study predicts loss of collagen fiber tension and increased matrix hydrostatic stress in those anular regions observed to undergo programmed cell death after 1 week of loading and ultimately become populated by chondrocytes after one month of recuperation. This correspondence conforms with the suggestions of othe rs that the cellular phenotype in collagenous tissues is sensitive to the d ominant type of tissue stress. Although the specific mechanisms by which al terations in tissue stress lead to apoptosis and variation in cell phenotyp e remain to be identified, our results suggest that maintenance of appropri ate stress within the disc may be an important basis for strategies to miti gate disc degeneration and initiate disc repair.