Compression-induced degeneration of the intervertebral disc : An in vivo mouse model and finite-element study

• Published in: Spine (Philadelphia, Pa. 1976) Pa. 1976), 1998-12, Vol.23 (23), p.2493-2506
• Main Authors: LOTZ, J. C, COLLIOU, O. K, CHIN, J. R, DUNCAN, N. A, LIEBENBERG, E
• Format: Article
• Language: English
• Subjects: Aggrecans; Animals; Apoptosis; Awards and Prizes; Biological and medical sciences; Cell Survival; Collagen - genetics; Collagen - metabolism; Disease Models, Animal; Extracellular Matrix Proteins; Finite Element Analysis; In Situ Nick-End Labeling; Intervertebral Disc - metabolism; Intervertebral Disc - pathology; Intervertebral Disc - physiopathology; Investigative techniques, diagnostic techniques (general aspects); Lectins, C-Type; Male; Medical sciences; Mice; Orthopedics; Osteoarticular system. Muscles; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pliability; Proteoglycans - genetics; Proteoglycans - metabolism; RNA, Messenger - biosynthesis; Space life sciences; Spinal Diseases - etiology; Spinal Diseases - metabolism; Spinal Diseases - physiopathology; Spine - pathology; Spine - surgery; Stress, Mechanical; Tail - pathology; Tail - surgery; Weight-Bearing - physiology
• ISSN: 0362-2436; 1528-1159
• DOI: 10.1097/00007632-199812010-00004

An in vivo study of the biologic and biomechanical consequences of static compressive loading on the mouse tail intervertebral disc. To determine whether static compression in vivo alters the biologic activity of the disc and leads to diminished biomechanical performance. Static compressive stress that exceeds the disc's swelling pressure is known to change hydration and the intradiscal stress distribution. Alterations in hydration and stress have been associated with changes in disc cell activity in vitro and in other collagenous tissues in vivo. Mouse tail discs were loaded in vivo with an external compression device. After 1 week at one of three different stress levels, the discs were analyzed for their biomechanical performance, morphology, cell activity, and cell viability. A second group of mice were allowed to recuperate for 1 month after the 1-week loading protocol to assess the disc's ability to recover. As an aid to interpreting the histologic and biologic data, finite-element analysis was used to predict region-specific changes in tissue stress caused by the static loading regimen. With increasing compressive stress, the inner and middle anulus became progressively more disorganized, and the percentage of cells undergoing 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 cellularity. 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 finite-element model, during sustained compression, tension is maintained in the outer anulus and lost in the inner and middle regions where the hydrostatic stress was predicted to increased nearly 10-fold. Discs loaded at the lowest stress recovered anular architecture but not cellularity after 1 month of recuperation. Discs loaded at the highest stress did not recover anular architecture, displaying islands of cartilage cells in the middle anulus at sites previously populated by fibroblasts. The results of the current project demonstrate that static compressive loading initiates a number of harmful responses in a dose-dependent way: disorganization of the anulus fibrosus; an increase in apoptosis and associated loss of cellularity; and down regulation of collagen II and aggrecan gene expression. The finite element model used in this study predicts loss of collage