Increased matrix synthesis following adenoviral transfer of a transforminggrowth factor beta(1) gene into articular chondrocytes

Monolayer cultures of lapine articular chondrocytes were transduced with fi rst-generation adenoviral Vectors carrying lacZ or transforming growth fact or beta(1) genes under the transcriptional control of the human cytomegalov irus early promoter. High concentrations of transforming growth factor beta (1) were produced by chondrocytes following transfer of the transforming gr owth factor beta(1) gene but not the lacZ gene. Transduced chondrocytes res ponded to the elevated endogenous production of transforming growth factor beta(1) by increasing their synthesis of proteoglycan, collagen, and noncol lagenous proteins in a dose-dependent fashion. The increases in collagen sy nthesis were not accompanied by alterations in the collagen phenotype; type II collagen remained the predominant collagen. Transforming growth factor beta(1) could not, however, rescue the collagen phenotype of cells that had undergone phenotypic modulation as a result of serial passaging. These dat a demonstrate that chondrocytes can be genetically manipulated to produce a nd respond to the potentially therapeutic cytokine transforming growth fact or beta(1). This technology has a number of experimental and therapeutic ap plications, including those related to the study and treatment of arthritis and cartilage repair.