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Increased matrix synthesis following adenoviral transfer of a transforming growth factor β 1 gene into articular chondrocytes
Author(s) -
Shuler Franklin D.,
Georgescu Helga I.,
Niyibizi Christopher,
Studer Rebecca K.,
Mi Zhibao,
Johnstone Brian,
Robbins Paul D.,
Evans Christopher H.
Publication year - 2000
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100180411
Subject(s) - transforming growth factor , growth factor , type ii collagen , microbiology and biotechnology , viral vector , cartilage , extracellular matrix , biology , proteoglycan , transforming growth factor beta , genetic enhancement , phenotype , chemistry , immunology , cancer research , gene , anatomy , biochemistry , receptor , recombinant dna
Monolayer cultures of lapine articular chondrocytes were transduced with first‐generation adenoviral vectors carrying lacZ or transforming growth factor β 1 genes under the transcriptional control of the human cytomegalovirus early promoter. High concentrations of transforming growth factor β 1 were produced by chondrocytes following transfer of the transforming growth factor β 1 gene but not the lacZ gene. Transduced chondrocytes responded to the elevated endogenous production of transforming growth factor β 1 by increasing their synthesis of proteoglycan, collagen, and noncollagenous proteins in a dose‐dependent fashion. The increases in collagen synthesis were not accompanied by alterations in the collagen phenotype; type‐II collagen remained the predominant collagen. Transforming growth factor β 1 could not, however, rescue the collagen phenotype of cells that had undergone phenotypic modulation as a result of serial passaging. These data demonstrate that chondrocytes can be genetically manipulated to produce and respond to the potentially therapeutic cytokine transforming growth factor β 1 . This technology has a number of experimental and therapeutic applications, including those related to the study and treatment of arthritis and cartilage repair.