[TGF-beta-1 gene transfer in joint cartilage cells. Stimulating effect in extracellular matrix synthesis].
TGF beta-1 has been shown to upregulate matrix synthesis in articular chondrocytes. TGF beta-gene transfer to chondrocytes has the potential to increase the local production of this key component within regenerating cartilage after trauma and could support the repair process in articular cartilage lesions. Primary rabbit articular chondrocytes were cultured and retrovirally transfected with the experimental TGF beta-1 and the lacZ marker gene for control purposes. After radioactive labeling of new synthesized matrix proteins results were compared with normal primary chondrocytes. After TGF beta-1 gene transfer the endogenous growth factor concentration was doubled compared to normal chondrocytes and decreased in the lacZ control group. The proteoglycan synthesis in TGF beta-1 transfected chondrocytes showed a 96% increase compared to the basal production of normal chondrocytes. The LacZ transfected group revealed the opposite effect by a 44% decrease. The collagen synthesis of TGF beta-1 transfected chondrocytes was 304% compared to normal chondrocytes, predominantly type II collagen. The lacZ group collagen production was reduced by 35%. We conclude that TGF beta-1 gene transfer overcomes the decreasing effect observed by transfection with the LacZ marker gene and increases matrix synthesis in articular chondrocytes. Genetically altered chondrocytes might improve the repair of cartilage lesions by stimulating matrix synthesis and supporting the expression of the hyaline phenotype.
Möller
H D
HD
Orthopädische Klinik, Medizinische Hochschule Hannover. moeller@annastift.de
Fu
F H
FH
Niyibizi
C
C
Studer
R K
RK
Georgescu
H J
HJ
Robbins
P D
PD
Evans
C H
CH
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D018014:Gene Transfer Techniques; D007763:Lac Operon / Q000235:genetics; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen