Complex loading affects intervertebral disc mechanics and biology.

BACKGROUND: Complex loading develops in multiple spinal motions and in the case of hyperflexion is known to cause intervertebral disc (IVD) injury. Few studies have examined the interacting biologic and structural alterations associated with potentially injurious complex loading, which may be an important contributor to chronic progressive degeneration. OBJECTIVE: This study tested the hypothesis that low magnitudes of axial compression loading applied asymmetrically can induce IVD injury affecting cellular and structural responses in a large animal IVD ex-vivo model. METHODS: Bovine caudal IVDs were assigned to either a control or wedge group (15°) and placed in organ culture for 7 days under static 0.2MPa load. IVD tissue and cellular responses were assessed through confined compression, qRT-PCR, histology and structural and compositional measurements, including Western blot for aggrecan degradation products. RESULTS: Complex loading via asymmetric compression induced cell death, an increase in caspase-3 staining (apoptosis), a loss of aggrecan and an increase in aggregate modulus in the concave annulus fibrosis. While an up-regulation of MMP-1, ADAMTS4, IL-1ß, and IL-6 mRNA, and a reduced aggregate modulus were induced in the convex annulus. CONCLUSION: Asymmetric compression had direct deleterious effects on both tissue and cells, suggesting an injurious loading regime that could lead to a degenerative cascade, including cell death, the production of inflammatory mediators, and a shift towards catabolism. This explant model is useful to assess how injurious mechanical loading affects the cellular response which may contribute to the progression of degenerative changes in large animal IVDs, and results suggest that interventions should address inflammation, apoptosis, and lamellar integrity.

Localized Intervertebral Disc Injury Leads to Organ Level Changes in Structure, Cellularity, and Biosynthesis.

A literature review and new data are presented to evaluate the influence of intervertebral disc (IVD) injury on biomechanics, cellularity, inflammation, and biosynthesis. Literature and new experimental evidence support the hypothesis that localized injury in the disc can lead to immediate and long-term organ level changes in biomechanics and biology of the IVD. Biomechanical properties defining motion segment bending behaviors sensitive to injuries that affect anulus fibrosus (AF) integrity and nucleus pulposus (NP) pressurization. Axial mechanics and IVD height measurements show sensitivity to puncture and other injuries that reduce NP pressurization. Torsional biomechanics are strongly affected by the extent and location of AF lesions but are less sensitive to reduced NP pressurization. IVD injuries such as puncture and stab incisions may also lead to a cascade of biological changes consistent with degeneration, including loss of cellularity, altered biosynthesis and inflammation. New results on effects of 25G needle injection of saline into a bovine IVD organ culture model demonstrated a loss of cellularity and down-regulation of matrix gene expression, providing a specific example of how a minor injury affects the IVD organ response. We conclude that localized injuries in the IVD can induce an organ level degenerative cascade through biomechanical and biological mechanisms, and their interactions. Attempts at IVD repair should target the dual biomechanical roles of the anulus of maintaining nucleus pressurization and transmitting loads across the vertebrae. Biologically, it remains important to maintain IVD cellularity and biosynthesis rates following injury to prevent downstream degenerative changes.