Research Output

Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity

  Bone development and length relies on the growth plate formation, which is dependent on degradative enzymes such as MMPs. Indeed, deletion of specific members of this enzyme family in mice results in important joint and bone abnormalities, suggesting a role in skeletal development. As such, the control of MMP activity is vital in the complex process of bone formation and growth. We generated a transgenic mouse line to overexpress TIMP3 in mouse chondrocytes using the Col2a1-chondrocyte promoter. This overexpression in cartilage resulted in a transient shortening of growth plate in homozygote mice but bone length was restored at eight weeks of age. However, tibial bone structure and mechanical properties remained compromised. Despite no transgene expression in adult osteoblasts from transgenic mice in vitro, their differentiation capacity was decreased. Neonates, however, did show transgene expression in a subset of bone cells. Our data demonstrate for the first time that transgene function persists in the chondro-osseous lineage continuum and exert influence upon bone quantity and quality.

  • Type:

    Article

  • Date:

    21 December 2016

  • Publication Status:

    Published

  • Publisher

    Public Library of Science (PLoS)

  • DOI:

    10.1371/journal.pone.0167971

  • ISSN:

    1932-6203

  • Library of Congress:

    QP Physiology

  • Dewey Decimal Classification:

    572 Biochemistry

  • Funders:

    Arthritis Research UK; Biotechnology and Biological Sciences Research Council; Orthopaedic Research UK

Citation

Poulet, B., Liu, K., Plumb, D., Vo, P., Shah, M., Staines, K., …Bou-Gharios, G. (2016). Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. PLoS ONE. 11(12), e0167971. doi:10.1371/journal.pone.0167971. ISSN 1932-6203

Authors

Copyright

© 2016 Poulet et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited

Keywords

Biochemistry, Genetics and Molecular Biology(all); Agricultural and Biological Sciences(all); Medicine(all)

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