TY - JOUR
T1 - Increased matrix synthesis following adenoviral transfer of a transforming growth factor β1 gene into articular chondrocytes
AU - Shuler, Franklin D.
AU - Georgescu, Helga I.
AU - Niyibizi, Christopher
AU - Studer, Rebecca K.
AU - Mi, Zhibao
AU - Johnstone, Brian
AU - Robbins, Paul D.
AU - Evans, Christopher H.
PY - 2000
Y1 - 2000
N2 - Monolayer cultures of lapine articular chondrocytes were transduced with first-generation adenoviral vectors carrying lacZ or transforming growth factor β1 genes under the transcriptional control of the human cytomegalovirus early promoter. High concentrations of transforming growth factor β1 were produced by chondrocytes following transfer of the transforming growth factor β1 gene but not the lacZ gene. Transduced chondrocytes responded to the elevated endogenous production of transforming growth factor β1 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 β1 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 β1. This technology has a number of experimental and therapeutic applications, including those related to the study and treatment of arthritis and cartilage repair.
AB - Monolayer cultures of lapine articular chondrocytes were transduced with first-generation adenoviral vectors carrying lacZ or transforming growth factor β1 genes under the transcriptional control of the human cytomegalovirus early promoter. High concentrations of transforming growth factor β1 were produced by chondrocytes following transfer of the transforming growth factor β1 gene but not the lacZ gene. Transduced chondrocytes responded to the elevated endogenous production of transforming growth factor β1 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 β1 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 β1. This technology has a number of experimental and therapeutic applications, including those related to the study and treatment of arthritis and cartilage repair.
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U2 - 10.1002/jor.1100180411
DO - 10.1002/jor.1100180411
M3 - Article
C2 - 11052495
AN - SCOPUS:0034232660
SN - 0736-0266
VL - 18
SP - 585
EP - 592
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 4
ER -