Dataset Information

Cyclic tensile stress exerts a protective effect on intervertebral disc cells.

ABSTRACT:

Objective

To examine the mechanisms behind the beneficial effects of motion-based therapies, the hypothesis that physiologic levels of tensile stress have a beneficial effect on annulus fibrosus cells was tested.

Design

To examine the roles of mechanical forces and inflammation in the intervertebral disc, changes in gene expression in response to inflammatory stimulus (IL-1 beta) and tensile stress (6% stress at 0.05 Hz) were examined in fibrochondrocytes isolated from the annulus fibrosus of Sprague-Dawley rats.

Results

Cells exposed to an inflammatory stimulus demonstrated an increase in catabolic gene expression, which decreased approximately 50% after exposure to both inflammatory stimulus and tensile stress. After exposure of cells to tensile stress alone, only matrix metalloprotease-13 showed a 50% decrease in expression. Collagen II showed a modest decrease in expression in response to tensile stress in the inflammatory environment. The expression of collagen I and aggrecan did not show a significant change under any of the conditions tested.

Conclusions

In this in vitro model, our data demonstrate that moderate levels of tensile stress act as a protective signal by decreasing the expression of catabolic mediators under conditions of inflammation. These data suggest that motion-based therapies that create tensile stress on the annulus may exert their beneficial effects through antiinflammatory actions.

SUBMITTER: Sowa G

PROVIDER: S-EPMC2935294 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Publications

Cyclic tensile stress exerts a protective effect on intervertebral disc cells.

Sowa Gwendolyn G Agarwal Sudha S

American journal of physical medicine & rehabilitation 20080701 7

<h4>Objective</h4>To examine the mechanisms behind the beneficial effects of motion-based therapies, the hypothesis that physiologic levels of tensile stress have a beneficial effect on annulus fibrosus cells was tested.<h4>Design</h4>To examine the roles of mechanical forces and inflammation in the intervertebral disc, changes in gene expression in response to inflammatory stimulus (IL-1 beta) and tensile stress (6% stress at 0.05 Hz) were examined in fibrochondrocytes isolated from the annulus ...[more]

PMID: 18209665

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Project description:Cellular senescence, characterized by a permanent state of cell cycle arrest and a secretory phenotype contributing to inflammation and tissue deterioration, has emerged as a target for age-related interventions. Accumulation of senescent cells is closely linked with intervertebral disc (IVD) degeneration, a prevalent age-dependent chronic disorder causing low back pain. Previous studies have highlighted that platelet-derived growth factor (PDGF) mitigated IVD degeneration through anti-apoptosis, anti-inflammation, and pro-anabolism. However, its impact on IVD cell senescence remains elusive. In this study, human NP and AF cells derived from aged, degenerated IVDs were treated with recombinant human (rh) PDGF-AB/BB for 5 days and changes of transcriptome profiling were examined through mRNA sequencing. NP and AF cells demonstrated similar but distinct responses to the treatment. However, the effects of PDGF-AB and BB on human IVD cells were comparable. Specifically, PDGF-AB/BB treatment resulted in downregulation of gene clusters related to neurogenesis and response to mechanical stimulus in AF cells while the downregulated genes in NP cells were mainly associated with metabolic pathways. In both NP and AF cells, PDGF-AB and BB treatment upregulated the expression of genes involved in cell cycle regulation, mesenchymal cell differentiation, and response to reduced oxygen levels, while downregulating the expression of genes related to senescence associated phenotype, including oxidative stress, reactive oxygen species (ROS), and mitochondria dysfunction. Network analysis revealed that PDGFRA and IL6 were the top hub genes in treated NP cells. Furthermore, in irradiation-induced senescent NP cells, PDGFRA gene expression was significantly reduced compared to non-irradiated cells. However, rhPDGF-AB/BB treatment increased PDGFRA expression and mitigated the senescence progression through increased cell population in the S phase, reduced SA-β-Gal activity, and decreased expression of senescence related regulators including P21, P16, IL6, and NF-κB. Our findings reveal a novel anti-senescence role of PDGF in the IVD, demonstrating its ability to alleviate the senescent phenotype and protect against the progression of senescence. This makes it a promising candidate for preventing or treating IVD degeneration by targeting cellular senescence.

Project description:IntroductionNucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from AC and annulus fibrosus (AF) cells, and to further determine their expression in normal and degenerate human intervertebral disc (IVD) cells.MethodsMicroarrays were conducted on bovine AC, AF and NP cells, using Affymetrix Genechip(R) Bovine Genome Arrays. Differential expression levels for a number of genes were confirmed by quantitative real time polymerase chain reaction (qRT-PCR) on bovine, AC, AF and NP cells, as well as separated bovine NP and notochordal (NC) cells. Expression of these novel markers were further tested on normal human AC, AF and NP cells, and degenerate AF and NP cells.ResultsMicroarray comparisons between NP/AC&AF and NP/AC identified 34 NP-specific and 49 IVD-specific genes respectively that were differentially expressed > or =100 fold. A subset of these were verified by qRT-PCR and shown to be expressed in bovine NC cells. Eleven genes (SNAP25, KRT8, KRT18, KRT19, CDH2, IBSP, VCAN, TNMD, BASP1, FOXF1 & FBLN1) were also differentially expressed in normal human NP cells, although to a lesser degree. Four genes (SNAP25, KRT8, KRT18 and CDH2) were significantly decreased in degenerate human NP cells, while three genes (VCAN, TNMD and BASP1) were significantly increased in degenerate human AF cells. The IVD negative marker FBLN1 was significantly increased in both degenerate human NP and AF cells.ConclusionsThis study has identified a number of novel genes that characterise the bovine and human NP and IVD transcriptional profiles, and allows for discrimination between AC, AF and NP cells. Furthermore, the similarity in expression profiles of the separated NP and NC cell populations suggests that these two cell types may be derived from a common lineage. Although interspecies variation, together with changes with IVD degeneration were noted, use of this gene expression signature will benefit tissue engineering studies where defining the NP phenotype is paramount.

Dataset Information

Cyclic tensile stress exerts a protective effect on intervertebral disc cells.

Objective

Design

Results

Conclusions

Publications

Cyclic tensile stress exerts a protective effect on intervertebral disc cells.

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