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Transforming growth factor-β1 (TGF-β1) regulates ATDC5 chondrogenic differentiation and fibronectin isoform expression

Authors

  • Fei Han,

    1. Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
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  • Christopher S. Adams,

    1. Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
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  • Zhuliang Tao,

    1. Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
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  • Charlene J. Williams,

    1. Department of Medicine, Division of Rheumatology, Thomas Jefferson University, Philadelphia, Pennsylvania
    2. Department of Biochemistry and Molecular Pharmacology and Jefferson Center for Biomedical Research, Thomas Jefferson University, Philadelphia, Pennsylvania
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  • Raihana Zaka,

    1. Department of Medicine, Division of Rheumatology, Thomas Jefferson University, Philadelphia, Pennsylvania
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  • Rocky S. Tuan,

    1. Cartilage Biology and Orthopaedics Branch, NIAMS, NIH, Bethesda, Maryland
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  • Pamela A. Norton,

    1. Department of Biochemistry and Molecular Pharmacology and Jefferson Center for Biomedical Research, Thomas Jefferson University, Philadelphia, Pennsylvania
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  • Noreen J. Hickok

    Corresponding author
    1. Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
    2. Department of Biochemistry and Molecular Pharmacology and Jefferson Center for Biomedical Research, Thomas Jefferson University, Philadelphia, Pennsylvania
    • Department of Orthopaedic Surgery, Thomas Jefferson University, 1015 Walnut St., Suite 501, Philadelphia, PA 19107.
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

Regulated splicing of fibronectin (FN) occurs during the mesenchymal to chondrocyte transition and ultimately results in the relative enrichment of an extra domain B (EDB) exon-containing FN isoform with the suggestion that FN isoforms may play a functional role in chondrogenesis. Promotion of chondrogenesis can also be achieved by treatment with transforming growth factor-β (TGF-β), which also regulates FN isoform expression. We have examined the effects of TGF-β treatment on the assumption of the chondrogenic phenotype in the teratoma-derived cell line ATDC5 and tested whether these effects on chondrogenesis are paralleled by appropriate changes in FN isoform expression. ATDC5 cells were maintained in a pre-chondrogenic state and, in this state, treated with 10 ng/ml TGF-β. The cells started to elaborate a matrix rich in sulfated proteoglycans, such that within the first 12 days of culture, TGF-β1 treatment appeared to slightly accelerate early acquisition of an Alcian blue-stained matrix, and caused a dose- and time-dependent decrease in collagen type I expression; changes in collagen type II expression were variable. At later times, cells treated with TGF-β became indistinguishable from those of the controls. Interestingly, TGF-β treatment caused a significant dose- and time-dependent decrease in the proportion of FN containing the extra domain A (EDA) and the EDB exons. These data suggest that TGF-β induces the early stages of chondrogenic maturation in this pre-chondrogenic line and that TGF-β treatment increases expression of FN isoforms that lack the EDA and EDB exons. Published 2005 Wiley-Liss, Inc.

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