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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-2-10
pubmed:abstractText
To develop new therapeutic options for the treatment of disc degeneration we tested the possibility of overexpression of active growth and differentiation factor (GDF) 5 and of transforming growth factor (TGF) beta(1) by adenoviral gene transfer and characterized its effect on cell proliferation and matrix synthesis of cultured rabbit and human intervertebral disc cells. Recombinant adenovirus encoding for GDF-5 or TGF-beta(1) was developed and transgene expression characterized by RT-PCR, western blot and ELISA. Growth and matrix synthesis of transduced cells was measured by [(3)H]thymidine or [(35)S]sulfate incorporation. Disc cells expressed the receptors BMPR1A, BMPR1B, and BMPR2, which are relevant for GDF-5 action. Adenovirus efficiently transferred the GDF-5 gene or the TGF-beta(1) gene to rabbit and human intervertebral disc cells. About 50 ng GDF-5 protein/10(6 )cells per 24 h or 7 ng TGF-beta(1) protein/10(6 )cells per 24 h was produced. According to western blotting, two GDF-5 forms, with molecular weights consistent with the activated GDF-5 dimer and the proform, were secreted over the 3 weeks following gene transfer. Overexpressed GDF-5 and TGF-beta(1) were bioactive and promoted growth of rabbit disc cells in monolayer culture. Our results suggest that ex vivo gene delivery of GDF-5 and TGF-beta(1) is an attractive approach for the release of mature and pre-GDF-5 in surrounding tissue. This leads us to hope that it will prove possible to improve the treatment of degenerative disc disease by means of ex vivo gene transfer of single or multiple growth factors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0946-2716
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
126-34
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:14669002-Adenoviridae, pubmed-meshheading:14669002-Animals, pubmed-meshheading:14669002-Bone Morphogenetic Protein Receptors, pubmed-meshheading:14669002-Bone Morphogenetic Proteins, pubmed-meshheading:14669002-Cell Culture Techniques, pubmed-meshheading:14669002-Cloning, Molecular, pubmed-meshheading:14669002-Flow Cytometry, pubmed-meshheading:14669002-Gene Expression, pubmed-meshheading:14669002-Gene Transfer Techniques, pubmed-meshheading:14669002-Green Fluorescent Proteins, pubmed-meshheading:14669002-Growth Differentiation Factor 5, pubmed-meshheading:14669002-Humans, pubmed-meshheading:14669002-Intervertebral Disc, pubmed-meshheading:14669002-Luminescent Proteins, pubmed-meshheading:14669002-Promoter Regions, Genetic, pubmed-meshheading:14669002-Proteoglycans, pubmed-meshheading:14669002-RNA, Messenger, pubmed-meshheading:14669002-Rabbits, pubmed-meshheading:14669002-Receptors, Growth Factor, pubmed-meshheading:14669002-Transforming Growth Factor beta
pubmed:year
2004
pubmed:articleTitle
Release of active and depot GDF-5 after adenovirus-mediated overexpression stimulates rabbit and human intervertebral disc cells.
pubmed:affiliation
Division of Experimental Orthopaedics, University of Heidelberg, Schlierbacher Landstrasse 200a, 69118, Heidelberg, Germany. wiltrud.richter@ok.uni-heidelberg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't