In vivo intervertebral disc remodeling: Kinetics of mRNA expression in response to a single loading event

MacLean, Jeffrey J.; Roughley, Peter J.; Monsey, Robert D.; Alini, Mauro; Iatridis, James C.

doi:10.1002/jor.20560

Cited by 25 publications

(38 citation statements)

References 34 publications

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“…Mechanically induced changes in AF and NP cell gene expressions were reported in rat tails (MacLean et al 2003(MacLean et al , 2008. In humans, a slight reduction in the apparent criss-cross angle of anterior AF fibres was reported with age (Hickey and Hukins 1982).…”

Section: Discussionmentioning

confidence: 95%

On the collagen criss-cross angles in the annuli fibrosi of lumbar spine finite element models

Noailly

Planell

Lacroix

2010

Biomech Model Mechanobiol

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In the human lumbar spine, annulus fibrosus fibres largely contribute to intervertebral disc stability. Detailed annulus models are therefore necessary to obtain reliable predictions of lumbar spine mechanics by finite element modelling. However, different definitions of collagen orientations coexist in the literature for healthy human lumbar annuli. Therefore, four annulus fibre-induced anisotropy models were built from reported anatomical descriptions, and inserted in a L3-L5 lumbar bi-segment finite element model. Annulus models were, respectively, characterized by radial, tangential, radial and tangential, and no fibre orientation gradients. The effect of rotational and axial compressive loadings was simulated and first, predictions were compared to experimental data. Then, intervertebral disc local biomechanics was studied under axial rotation and axial compression. A new parameter, i.e. the fibre contribution quality parameter, was computed in the anterior, lateral, postero-lateral, and posterior annuli of each model, in function of fibre stresses, radial load distributions, and matrix shear strains. Locally, each annulus model behaved differently, affecting intervertebral disc biomechanics and segmental motions. The fibre contribution quality parameter allowed establishing direct links between local annulus fibre organization and local annulus loadings, while other kinematical and biomechanical data did not. It was concluded that functional relations should exist between local annulus fibre orientations and overall segment morphology. The proposed fibre contribution quality parameter could be used to examine such relations and calibrate lumbar spine finite element models by locally adjusting the annulus bundle criss-cross angles. Conclusions of this study are particularly relevant to patient-specific models or artificial disc designs.

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Section: Discussionmentioning

confidence: 95%

On the collagen criss-cross angles in the annuli fibrosi of lumbar spine finite element models

Noailly

Planell

Lacroix

2010

Biomech Model Mechanobiol

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“…Loading time and analysis time were chosen accordingly to results in our pre-experiments and data from the literature. 15 …”

Section: Application Of Hydrostatic Pressure Under Controlled Osmolaritymentioning

confidence: 99%

Influence of extracellular osmolarity and mechanical stimulation on gene expression of intervertebral disc cells

Wuertz

Urban

Klasen

et al. 2007

Journal Orthopaedic Research

136

142

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Intervertebral discs (IVD) have a higher extracellular osmolarity than most other tissues; moreover their osmolarity changes by around 25% during each diurnal cycle. In this study, changes in aggrecan, collagen I and collagen II expression of IVD cells were examined after exposure to osmotic environment alterations or mechanical stimulation under different osmotic conditions. Human and bovine IVD cells seeded in three-dimensional (3D) collagen type I matrices were cultured under hypo-osmotic (300 mOsm), iso-osmotic (400 mOsm), or hyperosmotic (500 mOsm) conditions. Osmolarity-induced changes in gene expression of IVD cells were measured after 5 days. Loadinduced changes in gene expression under the different osmotic conditions were measured after application of hydrostatic pressure (0.25 MPa, 0.1 Hz, 30 min) or cyclic strain (4%, 1 Hz, 24 h). The results showed that IVD cells respond strongly to changes in the osmotic environment by altering mRNA expression. Human cells cultured over 5 days increased expression of aggrecan and collagen II in both nucleus and annulus cells under increasing osmolarity. In contrast, collagen I expression was inhibited at high osmolarity in both cell types. Mechanically induced alterations in gene expression appear to have only modest effects on matrix protein expression, but the same stimulus partly resulted in an inhibition or stimulation of gene expression, depending on the osmotic conditions. This study showed that the osmotic environment does not only have an appreciable effect on gene expression but also affects responses to mechanical stimuli. This suggests that the osmotic conditions cannot be ignored when examining physiological and pathological behavior of IVD cells.

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“…However, since TIMP-3 does not stimulate secretion of type II collagen directly, the way TIMP-3 improves matrix quality may be distinct from that of TGF-β1 gene transfection [25]. It may result from enhanced collagen protection by more sufficient aggrecan, which was provided by increased content of TIMP-3 [26]. Another possible cause for improvement of collagen quality was contributed to the anti-inflammatory effects of TIMP-3 [27,28].…”

Section: Discussionmentioning

confidence: 98%

Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral disc degeneration in vivo

Shao

Xiong

et al. 2009

Front. Med. China

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The aim of this study was to investigate the inhibitory effects of recombinant adenovirus vector carrying tissue inhibitor of metalloproteinase-3 (RAd-TIMP-3) against degeneration of rabbit intervertebral disc. Thirty Japanese white rabbits of 4 months old were randomly divided into 5 groups. Mild or moderate rabbit lumbar disc degeneration model was constructed with the controllable axial loading device by imposing 98 N pressure at the discs for 2 weeks. Various doses of virus were injected into the degenerated discs as follows: 20 μL of normal saline in group 1; 20 μL of RAd66 (an empty adenovirus vector, 1.0Â10 10 OPU/mL) in group 2; and 20, 10, and 5 μL of RAdTIMP-3 (1.0Â10 10 OPU/mL) in groups 3, 4, and 5, respectively. Two weeks after the injection, the discs were collected for investigations, including assessment of degeneration degrees according to the Thompson's grading system, reverse-transcription polymerase chain reaction (RT-PCR) assay for TIMP-3 gene, Safranin O-Fast green staining, and immunohistochemical staining for TIMP-3 and type II collagen. According to Thompson's criteria, the degeneration of groups 3, 4, and 5, especially group 3, was alleviated as compared with groups 1 and 2. RT-PCR revealed that the expression of TIMP-3 in groups 3, 4, and 5, especially in group 3, was significantly enhanced as compared with group 1 (P < 0.01). Both Safranin O-Fast green staining and type II collagen staining demonstrated better reserved integrity of disc matrix in groups 3, 4, and 5 than in groups 1 and 2. TIMP-3 staining exhibited an obvious increase of positive-staining rate in groups 3, 4, and 5 as compared with group 1. The positive-staining rate in group 3 (79.42%AE1.35%) was about 3 times that of group 1 (25.47%AE5.46%, P < 0.01). RAdTIMP-3 can effectively protect the matrix of rabbit intervertebral disc against overloading-induced degeneration in a dose-dependent manner, resulting in the alleviation of disc degeneration.

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In vivo intervertebral disc remodeling: Kinetics of mRNA expression in response to a single loading event

Cited by 25 publications

References 34 publications

On the collagen criss-cross angles in the annuli fibrosi of lumbar spine finite element models

On the collagen criss-cross angles in the annuli fibrosi of lumbar spine finite element models

Influence of extracellular osmolarity and mechanical stimulation on gene expression of intervertebral disc cells

Adenovirus-mediated tissue inhibitor of metalloproteinase-3 gene transfection inhibits rabbit intervertebral disc degeneration in vivo

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