Document Detail


Influence of low glucose supply on the regulation of gene expression by nucleus pulposus cells and their responsiveness to mechanical loading.
MedLine Citation:
PMID:  20887152     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECT: Environmental alterations resulting in a decrease in the nutrient supply have been associated with intervertebral disc (IVD) degeneration, particularly of the nucleus pulposus (NP). The goal of the present study was to examine the hypothesis that glucose deprivation alters the metabolism of NP cells and their responsiveness to mechanical loading. A possible interaction of glucose supply and hydrostatic pressure (HP) with gene expression by NP cells has not been investigated. METHODS: The influence of glucose supply (physiological concentration: 5 mM, reduction: 0 or 0.5 mM) and cyclic HP loading (2.5 MPa, 0.1 Hz, 30 minutes) on bovine and human NP cell matrix turnover was analyzed by quantitative real-time reverse transcriptase–polymerase chain reaction. Glucose-dependent effects on cell viability were determined by trypan blue exclusion. A glycosaminoglycan (GAG) assay was performed to determine nutritional effects on the protein level. RESULTS: Glucose reduction resulted in significant downregulations (p < 0.05) of aggrecan, collagen-I, and collagen-II gene expression by bovine NP cells. Exemplary human donors also displayed a similar trend for aggrecan and collagen-II, whereas matrix metalloproteinases (MMPs) tended to be upregulated under glucose deprivation. After HP loading, human NP cells showed individual upregulations of collagen-I and collagen-II expression, while MMP expression tended to be downregulated under glucose reduction relative to a normal glucose supply. Cell viability decreased with glucose deprivation. The GAG content was similar in all groups at Day 1, whereas at Day 3 there was a significant increase under physiological conditions. CONCLUSIONS: Glucose deprivation strongly affected NP cell metabolism. The effects of an altered glucose supply on gene expression were more pronounced than the mechanically induced effects. Data in this study demonstrate that the glucose environment is more critical for disc cell metabolism than mechanical loads. In individual human donors, however, adequate mechanical stimuli might have a beneficial effect on matrix turnover during IVD degeneration.
Authors:
Christina Rinkler; Frank Heuer; Maria Teresa Pedro; Uwe Max Mauer; Anita Ignatius; Cornelia Neidlinger-Wilke
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurosurgery. Spine     Volume:  13     ISSN:  1547-5646     ISO Abbreviation:  J Neurosurg Spine     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101223545     Medline TA:  J Neurosurg Spine     Country:  United States    
Other Details:
Languages:  eng     Pagination:  535-42     Citation Subset:  IM    
Affiliation:
Institute of Orthopaedic Research and Biomechanics, Centre for Musculoskeletal Research, University of Ulm, Ulm, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aggrecans / metabolism
Animals
Cattle
Cell Survival
Cells, Cultured
Collagen / metabolism
Computer Systems
Down-Regulation
Female
Gene Expression*
Glucose / deficiency*
Glycosaminoglycans / analysis
Humans
Hydrostatic Pressure*
Intervertebral Disk / chemistry,  cytology,  metabolism*
Male
Matrix Metalloproteinases / metabolism
Middle Aged
RNA / analysis
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation
Young Adult
Chemical
Reg. No./Substance:
0/Aggrecans; 0/Glycosaminoglycans; 50-99-7/Glucose; 63231-63-0/RNA; 9007-34-5/Collagen; EC 3.4.24.-/Matrix Metalloproteinases

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