Complex loading affects intervertebral disc mechanics and biology

Abstract

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 0.2 MPa 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-1β, 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.

Inflammation in intervertebral disc degeneration and regeneration

“…Apart from in vitro studies, organ cultures of bovine caudal IVDs have shown that compression induces apoptosis, produces inflammatory mediators and alters matrix integrity, leading to development of the disease [96].…”

Transcriptional profiling distinguishes inner and outer annulus fibrosus from nucleus pulposus in the bovine intervertebral disc

“…Therefore, model organisms, such as the cow, are used for in vitro cellular and ex vivo biomechanical studies of the IVD [14,15]. The bovine tail IVD represents a good model for the non-degenerate human IVD: the bovine NP retains few notochordal cells and whole transcriptome analyses identified similar phenotypic marker genes as in humans [6,16,17].…”

Lumbar annulus fibrosus biomechanical characterization in healthy children by ultrasound shear wave elastography

“…The disc -particularly the nucleus -becomes less gelatinous and more fibrous, and cracks and fissures eventually form. In AIS patients, minor histological alterations of the disc can be observed as soon as 3-7 years of age and they significantly increase after 16 years of age [8]; asymmetric loading, which is characteristic of scoliosis, can add to the detrimental effects of aging on disc biology [9].…”