Abstract
Low-back pain (LBP) is a common medical complaint and associated with high societal costs. Degeneration of the intervertebral disc (IVD) is assumed to be an important causal factor of LBP. IVDs are continuously mechanically loaded and both positive and negative effects have been attributed to different loading conditions.In order to study mechanical loading effects, degeneration-associated processes and/or potential regenerative therapies in IVDs, it is imperative to maintain the IVDs' structural integrity. While in vivo models provide comprehensive insight in IVD biology, an accompanying organ culture model can focus on a single factor, such as loading and may serve as a prescreening model to reduce life animal testing. In the current study we examined the feasibility of organ culture of caprine lumbar discs, with the hypothesis that a simulated-physiological load will optimally preserve IVD properties.Lumbar caprine IVDs (n = 175) were cultured in a bioreactor up to 21 days either without load, low dynamic load (LDL), or with simulated-physiological load (SPL). IVD stiffness was calculated from measurements of IVD loading and displacement. IVD nucleus, inner- and outer annulus were assessed for cell viability, cell density and gene expression. The extracellular matrix (ECM) was analyzed for water, glycosaminoglycan and total collagen content.IVD biomechanical properties did not change significantly with loading conditions. With SPL, cell viability, cell density and gene expression were preserved up to 21 days. Both unloaded and LDL resulted in decreased cell viability, cell density and significant changes in gene expression, yet no differences in ECM content were observed in any group.In conclusion, simulated-physiological loading preserved the native properties of caprine IVDs during a 21-day culture period. The characterization of caprine IVD response to culture in the LDCS under SPL conditions paves the way for controlled analysis of degeneration- and regeneration-associated processes in the future.
Highlights
Low-back pain (LBP) is the most common medical complaint in Western society, possibly leading to an incapacitating condition and encompassing considerable ensuing socio-economic costs [1]
Intervertebral disc (IVD) at levels L1–L2 and L5–L6 showed larger deviations in calculated cross-sectional area, these IVDs were used as day 0 controls or unloaded culture controls
When comparing the anabolic gene expressions of the unloaded and low dynamic load (LDL) group to the simulatedphysiological load (SPL) group, we found that collagen 2b, aggrecan and biglycan are significantly down-regulated in both nucleus and outer annulus
Summary
Low-back pain (LBP) is the most common medical complaint in Western society, possibly leading to an incapacitating condition and encompassing considerable ensuing socio-economic costs [1]. Intervertebral disc (IVD) degeneration, or degenerative disc disease (DDD), has been associated with LBP [2,3,4,5] and recent large population based studies provide strong evidence for their correlation [6]. Various new treatment strategies are being developed to halt the progression of degeneration or even to regenerate the intervertebral disc. This is challenging as DDD itself is considered a multi factorial process [12]. Mechanical loading of the intervertebral disc is considered to be a major extrinsic cause of intervertebral disc degeneration [25,26,27,28]. Mechanical loading is a natural stimulus to chondrocytes and regarded to be essential for maintenance of the cartilaginous matrix [25,29,30,31,32,33,34]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
