Regulation of Gdf5 expression in joint remodelling, repair and osteoarthritis

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  • Karolina Kania, University of Aberdeen, United Kingdom
  • Fabio Colella, University of Aberdeen, United Kingdom
  • Anna H.K. Riemen, University of Aberdeen, United Kingdom
  • Hui Wang, University of Aberdeen, United Kingdom
  • Ken Howard
  • Thomas Aigner, Department of Pathology and Molecular Pathology, Medical Center Coburg, Coburg, Germany
  • ,
  • Francesco Dell’Accio, Queen Mary University of London, United Kingdom
  • Terence D. Capellini, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA, United States
  • Anke J. Roelofs, University of Aberdeen, United Kingdom
  • Cosimo De Bari, University of Aberdeen, United Kingdom

Growth and Differentiation Factor 5 (GDF5) is a key risk locus for osteoarthritis (OA). However, little is known regarding regulation of Gdf5 expression following joint tissue damage. Here, we employed Gdf5-LacZ reporter mouse lines to assess the spatiotemporal activity of Gdf5 regulatory sequences in experimental OA following destabilisation of the medial meniscus (DMM) and after acute cartilage injury and repair. Gdf5 expression was upregulated in articular cartilage post-DMM, and was increased in human OA cartilage as determined by immunohistochemistry and microarray analysis. Gdf5 expression was also upregulated during cartilage repair in mice and was switched on in injured synovium in prospective areas of cartilage formation, where it inversely correlated with expression of the transcriptional co-factor Yes-associated protein (Yap). Indeed, overexpression of Yap suppressed Gdf5 expression in chondroprogenitors in vitro. Gdf5 expression in both mouse injury models required regulatory sequence downstream of Gdf5 coding exons. Our findings suggest that Gdf5 upregulation in articular cartilage and synovium is a generic response to knee injury that is dependent on downstream regulatory sequence and in progenitors is associated with chondrogenic specification. We propose a role for Gdf5 in tissue remodelling and repair after injury, which may partly underpin its association with OA risk.

Original languageEnglish
Article number157
JournalScientific Reports
Volume10
Issue1
Pages (from-to)157
Number of pages11
ISSN2045-2322
DOIs
Publication statusPublished - 13 Jan 2020

    Research areas

  • ALLELIC EXPRESSION, ARTICULAR-CARTILAGE FORMATION, BRACHYPODISM, GROWTH, MICE, MORPHOGENESIS, MUTATIONS, PROTEINS, SUSCEPTIBILITY, SYNOVIAL JOINT

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