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Degenerative Grade Affects the Responses of Human Nucleus Pulposus Cells to Link-N, CTGF, and TGFβ3.
MedLine Citation:
PMID:  22907063     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
STUDY DESIGN:: Cells isolated from moderately and severely degenerated human intervertebral discs (IVDs) cultured in an alginate scaffold. OBJECTIVE:: To compare the regenerative potential of moderately vs. severely degenerated cells using three pro-anabolic stimulants. SUMMARY OF BACKGROUND DATA:: Injection of soluble cell signaling factors has potential to slow the progression of IVD degeneration. While 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:: NP cells were cultured in alginate for 21 days and treated with three different pro-anabolic stimulants: a growth factor/anti-inflammatory combination of TGFβ3+Dex, or matricellular proteins CTGF or Link-N. They were assayed for metabolic activity, DNA content, glycosaminoglycan (GAG), 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 to 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 up-regulated 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 GAG. CONCLUSION:: Pro-anabolic stimulants alone had limited capacity to overcome the catabolic and pro-inflammatory 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     Date:  2012-8-18
Journal Detail:
Title:  Journal of spinal disorders & techniques     Volume:  -     ISSN:  1539-2465     ISO Abbreviation:  J Spinal Disord Tech     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140323     Medline TA:  J Spinal Disord Tech     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*School of Engineering, University of Vermont, Burlington, VT †Leni and Peter May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY ‡Department of Orthopaedics & Rehabilitation, University of Vermont, Burlington, VT §Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH.
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