Fibroblast growth factor-2 induced chondrocyte cluster formation in experimentally wounded articular cartilage is blocked by soluble Jagged-1

Khan, Ilyas Mahmood, Palmer, Elizabeth and Archer, Charles William 2010. Fibroblast growth factor-2 induced chondrocyte cluster formation in experimentally wounded articular cartilage is blocked by soluble Jagged-1. Osteoarthritis and Cartilage 18 (2) , pp. 208-219. 10.1016/j.joca.2009.08.011

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Abstract

Basic fibroblast growth factor (FGF2) is a mitogen for articular chondrocytes. Cell death frequently occurs upon cartilage wounding and is evident during the progression of osteoarthritis. We hypothesised that incubation of wounded articular cartilage with exogenously added FGF2 would enhance cartilage repair, replacing dead cells through increased cell proliferation. Articular cartilage from the metacarapalphalangeal joint of immature bovine steers was wounded in situ, then incubated in vitro in the continual presence or absence of FGF2. Cellular proliferation was expressed as a ratio of cell density of a fixed area between wounded and adjacent cartilage. Immunolabelling revealed the incorporation of bromodeoxyuridine and localisation of collagen type VI and Notch1 epitopes. γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester and soluble Jagged1 ligand (sJ1) were used to analyse the function of Notch signalling in this wound model. FGF2 induced cellular proliferation at the margins of wounded articular cartilage, where proliferative chondrocytes adopted a cluster configuration. Collagen type VI protein was expressed by chondrocytes in clusters, as was Notch1. Cellular proliferation was not affected by inhibition of γ-secretase dependent Notch1 signalling. Binding of sJ1 to Notch1 receptors in FGF2 treated cartilage inhibited proliferation. Addition of FGF2 induces rapid chondrocyte proliferation in wounded cartilage, chondrocytes adopt a cluster morphology and also express Notch1. Binding of sJ1 to Notch1 causes apoptosis overriding a proliferative response. This study may shed some light on the significance of increased Notch1 expression and its localisation in chondrocyte clusters in osteoarthritic cartilage.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Biosciences
Subjects:	Q Science > Q Science (General) R Medicine > R Medicine (General)
Publisher:	Elsevier
ISSN:	1063-4584
Last Modified:	05 Feb 2020 21:07
URI:	https://orca.cardiff.ac.uk/id/eprint/19638

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