Reduced nucleus pulposus glycosaminoglycan content alters intervertebral disc dynamic viscoelastic mechanics

Abstract

The intervertebral disc functions over a range of dynamic loading regimes including axial loads applied across a spectrum of frequencies at varying compressive loads. Biochemical changes occurring in early degeneration, including reduced nucleus pulposus glycosaminoglycan content, may alter disc mechanical behavior and thus may contribute to the progression of degeneration. The objective of this study was to determine disc dynamic viscoelastic properties under several equilibrium loads and loading frequencies, and further, to determine how reduced nucleus glycosaminglycan content alters dynamic mechanics. We hypothesized (1) that dynamic stiffness would be elevated with increasing equilibrium load and increasing frequency, (2) that the disc would behave more elastically at higher frequencies, and finally, (3) that dynamic stiffness would be reduced at low equilibrium loads under all frequencies due to nucleus glycosaminoglycan loss. We mechanically tested control and chondroitinase-ABC injected rat lumbar motion segments at several equilibrium loads using oscillatory loading at frequencies ranging from 0.05 to 5 Hz. The rat lumbar disc behaved non-linearly with higher dynamic stiffness at elevated compressive loads irrespective of frequency. Phase angle was not affected by equilibrium load, although it decreased as frequency was increased. Reduced glycosaminoglycan decreased dynamic stiffness at low loads but not at high equilibrium loads and led to increased phase angle at all loads and frequencies. The findings of this study demonstrate the effect of equilibrium load and loading frequencies on dynamic disc mechanics and indicate possible mechanical mechanisms through which disc degeneration can progress.

Modeling Degenerative Disk Disease in the Lumbar Spine: A Combined Experimental, Constitutive, and Computational Approach

“…While the role of fluid flow in the degeneration cascade has not been explicitly determined, known changes [52][53][54] in the endplate and annulus permeability with age indicate that fluid fiow may play an important part in this process. These alterations in the mechanical contribution of the fiuid component as well as the interaction between the solid and fiuid phases may potentially change the time-dependent behavior of the disk (such as relaxation or creep) [55]. Modeling of these phenomena would add substantial complexity to the model, and should be included in future work.…”

Delivering Mesenchymal Stem Cells in Collagen Microsphere Carriers to Rabbit Degenerative Disc: Reduced Risk of Osteophyte Formation

“…51,56 This frequency-dependent change in dynamic stiffness was lost when the NP was removed by puncture injury 57,58 but the loss was prevented when injecting silicon polymers with suitable mechanical properties into the disc. 59 Moreover, frequency-dependent changes in disc dynamic stiffness have been associated with extracellular matrix component changes upon protease digestion and crosslinking treatment in rat spinal motion segments 45 while chondroitinase-ABC-induced degenerative disc was found with lower GAG content and lower dynamic stiffness, 60 both suggesting that dynamic mechanical analysis of the disc is a sensitive parameter revealing changes in matrix structural and compositional changes. In the current study, the presence of the collagen matrix and the fluid effect may produce a stiffening effect, contributing to the frequencydependent dynamic mechanical properties.…”

Reconstruction of an In Vitro Niche for the Transition from Intervertebral Disc Development to Nucleus Pulposus Regeneration

“…Biochemical changes occurring in early degeneration, including a reduced GAG content in the NP, may alter the disc mechanical behavior and contribute to the progression of degeneration [90]. Other than hydrostatic pressure, the NP also experiences high interstitial fluid and osmotic pressure during loading that arises from a high fluid content and PGassociated negative charges [91,92].…”