Systems genetics analysis of mouse chondrocyte differentiation

Authors

  • Jaijam Suwanwela,

    Corresponding author
    1. Department of Oral Biology, School of Dentistry, UCLA, Los Angeles, CA, USA
    2. Department of Prosthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
    • Department of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, CA 90095, USA.
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  • Charles R Farber,

    1. Center for Public Health Genomics, Departments of Medicine and Biochemistry and Molecular Biology, University of Virginia, Charloltesville, VA, USA
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  • Bau-lin Haung,

    1. Department of Oral Biology, School of Dentistry, UCLA, Los Angeles, CA, USA
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  • Buer Song,

    1. Department of Molecular, Cell, and Developmental Biology and Department of Orthopedic Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
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  • Calvin Pan,

    1. Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
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  • Karen M Lyons,

    1. Department of Molecular, Cell, and Developmental Biology and Department of Orthopedic Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
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  • Aldons J Lusis

    1. Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
    2. Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
    3. Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
    4. Molecular Biology Institute, UCLA, Los Angeles, CA, USA
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Abstract

One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research.

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