Document Detail


Degenerative grade affects the responses of human nucleus pulposus cells to link-N, CTGF, and TGFβ3.
MedLine Citation:
PMID:  22907063     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
STUDY DESIGN: Cells isolated from moderately and severely degenerated human intervertebral disks (IVDs) cultured in an alginate scaffold.
OBJECTIVE: To compare the regenerative potential of moderately versus severely degenerated cells using 3 proanabolic stimulants.
SUMMARY OF BACKGROUND DATA: Injection of soluble cell signaling factors has potential to slow the progression of IVD degeneration. Although degenerative grade is thought to be an important factor in targeting therapeutic interventions it remains unknown whether cells in severely degenerated IVDs have impaired metabolic functions compared to lesser degenerative levels or if they are primarily influenced by the altered microenvironment.
METHODS: Nucleus pulposus (NP) cells were cultured in alginate for 21 days and treated with 3 different proanabolic stimulants: a growth factor/anti-inflammatory combination of transforming growth factor β3 (TGFβ3)+dexamethasone (Dex), or matricellular proteins connective tissue growth factor (CTGF) or Link-N. They were assayed for metabolic activity, DNA content, glycosaminoglycan, and qRT-PCR gene profiling.
RESULTS: Moderately degenerated cells responded to stimulation with increased proliferation, decreased IL-1β, MMP9, and COL1A1 expression, and upregulated HAS1 as compared with severely degenerated cells. TGFβR1 (ALK5) receptors were expressed at greater levels in moderately than severely degenerated cells. TGFβ3+Dex had a notable stimulatory effect on moderately degenerated NP cells with increased anabolic gene expression and decreased COL1A1 and ADAMTS5 gene expression. Link-N and CTGF had similar responses in all assays, and both treatments upregulated IL-1β expression and had a more catabolic response than TGFβ3+Dex, particularly in the more severely degenerated group. All groups, including different degenerative grades, produced similar amounts of glycosaminoglycan.
CONCLUSIONS: Proanabolic stimulants alone had limited capacity to overcome the catabolic and proinflammatory cytokine expression of severely degenerated NP cells and likely require additional anti-inflammatory treatments. Moderately degenerated NP cells had greater TGFβ receptor 1 expression and better responded to anabolic stimulation.
Authors:
Rosalyn D Abbott; Devina Purmessur; Robert D Monsey; David R Brigstock; Damien M Laudier; James C Iatridis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of spinal disorders & techniques     Volume:  26     ISSN:  1539-2465     ISO Abbreviation:  J Spinal Disord Tech     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-26     Completed Date:  2013-11-08     Revised Date:  2014-05-09    
Medline Journal Info:
Nlm Unique ID:  101140323     Medline TA:  J Spinal Disord Tech     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E86-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Proliferation / drug effects
Cells, Cultured
Collagen Type I / genetics,  metabolism
Connective Tissue Growth Factor / pharmacology
Dexamethasone / pharmacology
Female
Humans
Interleukin-1beta / genetics,  metabolism
Intervertebral Disc / drug effects*,  metabolism,  pathology
Intervertebral Disc Degeneration / metabolism,  pathology*
Male
Matrix Metalloproteinase 9 / genetics,  metabolism
Middle Aged
Protein-Serine-Threonine Kinases / genetics,  metabolism
Receptors, Transforming Growth Factor beta / genetics,  metabolism
Severity of Illness Index
Transforming Growth Factor beta3 / pharmacology
Grant Support
ID/Acronym/Agency:
R01 AR051146/AR/NIAMS NIH HHS; R01AR051146/AR/NIAMS NIH HHS; R21 AR056037/AR/NIAMS NIH HHS; R21AR056037/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/CTGF protein, human; 0/Collagen Type I; 0/Interleukin-1beta; 0/Receptors, Transforming Growth Factor beta; 0/Transforming Growth Factor beta3; 0/collagen type I, alpha 1 chain; 139568-91-5/Connective Tissue Growth Factor; 7S5I7G3JQL/Dexamethasone; EC 2.7.1.11/TGF-beta type I receptor; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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