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Regulation of Gdf5 expression in joint remodelling, repair and osteoarthritis
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Regulation of Gdf5 expression in joint remodelling, repair and osteoarthritis
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Journal Article
Regulation of Gdf5 expression in joint remodelling, repair and osteoarthritis
2020
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/109
/ 13/51
/ 14/19
/ 14/63
/ 38/39
/ 38/61
/ 38/77
/ 631/532
/ 64/60
/ Animals
/ Cartilage, Articular - injuries
/ Cartilage, Articular - metabolism
/ Cartilage, Articular - pathology
/ Exons
/ Female
/ Genetic Predisposition to Disease
/ Growth differentiation factor 5
/ Growth Differentiation Factor 5 - genetics
/ Growth Differentiation Factor 5 - metabolism
/ Humanities and Social Sciences
/ Humans
/ Male
/ Meniscus
/ Mice
/ Science
/ Synovium
