Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs.

Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Research Abstract Details 

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Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Abstract Text:

Corey J Wallach,Satoshi Sobajima,Yasuhiko Watanabe,Joseph S Kim,Helga I Georgescu,Paul Robbins,Lars G Gilbertson,James D Kang,

STUDY DESIGN: Cells from degenerated intervertebral discs were transduced with an adenoviral vector delivering cDNA of the catabolic inhibitor, TIMP-1, and alterations in the measured proteoglycan were assessed. OBJECTIVES: To assess the potential of TIMP-1 to favorably modify the proteoglycan content of degenerated intervertebral disc cells. SUMMARY OF BACKGROUND DATA: Gene therapy with anabolic factors has resulted in increased proteoglycan synthesis in intervertebral disc cells. Biochemical analysis of degenerated discs has revealed elevated levels of the catabolic enzymes, matrix metalloproteinase, suggesting an intimate role of these factors in the degenerative process. The use of TIMP-1, an endogenous inhibitor of matrix metalloproteinase, via gene therapy may provide an additional method to alter the degenerative processes occurring in the intervertebral disc. MATERIALS AND METHODS: Degenerated intervertebral disc were isolated from eight patients undergoing elective surgical procedures. Cells were cultured in monolayer and transduced with different concentrations of either an adenoviral-tissue inhibitor of metalloproteinase-1 (Ad-TIMP-1) or adenoviral-bone morphogenic protein-2 (Ad-BMP-2) construct. Cells were cultured in a three-dimensional pellet and proteoglycan synthesis was assessed via 35S-sulfur incorporation. RESULTS: Gene delivery of TIMP-1 and BMP-2 increased measured proteoglycan synthesis at each concentration assessed. IVD cells treated with Ad-TIMP-1 demonstrated an optimal response at a multiplicity of infection (MOI) of 100. Cells treated with Ad-BMP-2 demonstrated a progressive increase in proteoglycan synthesis with increasing viral concentrations. CONCLUSIONS: Successful delivery of the anticatabolic gene, TIMP-1, results in increased measured proteoglycan in cultured degenerated disc cells. This finding supports catabolic inhibition as a promising avenue of research for the treatment of degenerative disc disease via gene therapy.

Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Publishing Authors By Initials

CJ Wallach,S Sobajima,Y Watanabe,JS Kim,HI Georgescu,P Robbins,LG Gilbertson,JD Kang,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Spine

VOLUME: 28

Page Numbers: 2331-7

Journal Abbreviation: Spine

ISSN: 1528-1159

DAY: 15

MONTH: Oct

YEAR: 2003

Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Information

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LANGUAGE: eng

NlmUniqueID: 7610646

Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: metabolism

Chemical & Substance for Abstract: Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Information

Substance Name: bone morphogenetic protein 2

Registry Number: 0

Grant and Affiliation Information for Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs.

AFFILIATION: Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

Country: United States

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MEDLINETA: Spine

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