Journal article
Transforming growth factor-β1 regulates fibronectin isoform expression and splicing factor SRp40 expression during ATDC5 chondrogenic maturation
Experimental cell research, v 313(8), pp 1518-1532
2007
PMID: 17391668
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Fibronectin (FN) isoform expression is altered during chondrocyte commitment and maturation, with cartilage favoring expression of FN isoforms that includes the type II repeat extra domain B (EDB) but excludes extra domain A (EDA). We and others have hypothesized that the regulated splicing of FN mRNAs is necessary for the progression of chondrogenesis. To test this, we treated the pre-chondrogenic cell line ATDC5 with transforming growth factor-β1, which has been shown to modulate expression of the EDA and EDB exons, as well as the late markers of chondrocyte maturation; it also slightly accelerates the early acquisition of a sulfated proteoglycan matrix without affecting cell proliferation. When chondrocytes are treated with TGF-β1, the EDA exon is preferentially excluded at all times whereas the EDB exon is relatively depleted at early times. This regulated alternative splicing of FN correlates with the regulation of alternative splicing of SRp40, a splicing factor facilitating inclusion of the EDA exon. To determine if overexpression of the SRp40 isoforms altered FN and FN EDA organization, cDNAs encoding these isoforms were overexpressed in ATDC5 cells. Overexpression of the long-form of SRp40 yielded an FN organization similar to TGF-β1 treatment; whereas overexpression of the short form of SRp40 (which facilitates EDA inclusion) increased formation of long-thick FN fibrils. Therefore, we conclude that the effects of TGF-β1 on FN splicing during chondrogenesis may be largely dependent on its effect on SRp40 isoform expression.
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Details
- Title
- Transforming growth factor-β1 regulates fibronectin isoform expression and splicing factor SRp40 expression during ATDC5 chondrogenic maturation
- Creators
- Fei Han - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USAJames R Gilbert - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USAGerald Harrison - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USAChristopher S Adams - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USATheresa Freeman - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USAZhuliang Tao - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USARaihana Zaka - Division of Rheumatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USAHongyan Liang - Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, PA 19107, USACharlene Williams - Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, PA 19107, USARocky S Tuan - Cartilage Biology and Orthopaedics Branch, NIAMS, NIH, Bethesda, MD 20892-8022, USAPamela A Norton - Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, PA 19107, USANoreen J Hickok - Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA
- Publication Details
- Experimental cell research, v 313(8), pp 1518-1532
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000246128300002
- Scopus ID
- 2-s2.0-34247139808
- Other Identifier
- 991014878010604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Oncology