Dynamic Compression Effects on Intervertebral Disc Mechanics and Biology

Experimental evidence points to a threshold of loading necessary for intervertebral disc (IVD) extracellular matrix maintenance, where too little load (i.e., immobilization) will reduce biosynthesis rates and overloading can cause structural damage and altered biomechanical behaviors.1-3 Dynamic loading is commonly experienced during daily activity, and is particularly important to include when attempting to identify loading patterns that introduce risks to IVD structure, biomechanics, and biosynthesis. Furthermore, a cyclic loading component is necessary to distinguish between immobilization and overloading. In vivo studies demonstrated there is a frequency, magnitude, and duration effect of applied mechanical loading on IVD cells,2,4 further supporting the importance of a better understanding of such loading patterns on the IVD. The motion segment complex provides 6 degree of freedom mobility, but its structural components are sensitive to damage under distinct loading conditions. Complex loading regimes (e.g., bending and compression), on the spine can result in disc damage and herniation.3,5-8 Compression loading on the spine is known to put the vertebral endplate at risk of fracture, which is then associated with a loss of nucleus pressurization because of damage at the discovertebral junction.6,9 Evidence of biologic remodeling in disc tissue occurs in response to compressive loading magnitudes insufficient to cause vertebral endplate failure,2 raising the possibility that thresholds of structural failure overestimate the levels of loading which are detrimental to intervertebral disc health. The biologic response of the IVD to dynamic loading has been previously examined in vivo1,2,10-12 and in cell culture studies,4,13,14 whereas the effects of mechanical loading on IVD structure and mechanics have been studied extensively on nonviable tissue in vitro, leaving unanswered questions about the effects of such mechanical changes on living cell populations. Mechanical loading is known to influence the IVD; however, unanswered questions remain regarding the dependence on other signaling pathways existing in vivo (e.g., proinflammatory molecules), and whether the loss of cell-tissue matrix contact in vitro is detrimental to normal mechanical signal transduction. The ability to examine biologic remodeling pathways while also quantifying structural and mechanical changes induced in response to mechanical loading is a critical step towards understanding how the relationship between biomechanical loading and biologic remodeling might contribute toward a progressive degenerative cascade in the IVD. The use of an organ culture model facilitates investigation into cellular responses to mechanical loading while the disc is largely intact. Organ culture provides complete control over mechanical boundary conditions while allowing for measurement of mechanical properties throughout the culture duration. Chemical boundary conditions can also be controlled, eliminating the effect of other signaling pathways present in vivo, while maintaining viable cells and normal cell-matrix interactions. Currently, however, few studies have investigated the response of the IVD in organ culture to dynamic loading. Developing and testing a large animal organ culture system is important because of its ability to be more directly translated to human IVDs and also because of the ability to evaluate multiple mechanical and biologic dependent variables on the same IVD. The aim of this study was to examine the effects of varying physiologic magnitudes of dynamic compression on intact intervertebral disc structure, biomechanics, cell metabolism, and water content in 3 disc regions. The hypotheses were that low magnitudes of dynamic compression would enhance anabolic remodeling whereas high magnitudes of dynamic compression would demonstrate early signs of disc damage and catabolic remodeling. Specifically, dynamic compression applied to the intervertebral disc structure at low magnitudes of active physiologic loading in a human (0.2–1 MPa, e.g., standing up from a chair15) will promote anabolic remodeling, including increased biosynthesis rates, whereas loading at larger magnitudes of active physiologic loading in a human (0.2–2.5 MPa, e.g., lifting 20 kg with round back15 but less than failure of bovine caudal motion segment16,17) will result in early signs of remodeling including structural damage, loss of cell viability, and catabolic remodeling as measured through biomechanical properties, histology, biochemical measurements, sulfate incorporation, and qRT-PCR.