Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice

Human Molecular Genetics
G Valverde-FrancoJanet E Henderson

Abstract

Fibroblast growth factor (FGF) receptor 3 has been identified as a key regulator of endochondral bone development and of post-natal bone metabolism through its action on growth plate chondrocytes and osteoblasts, respectively. It has also been shown to promote chondrogenesis and cartilage production by cultured pre-chondrogenic cells in response to FGF18. In the current studies, we show that the absence of signaling through Fgfr3 in the joints of Fgfr3(-/-) mice leads to premature cartilage degeneration and early arthritis. Degenerative changes in cartilage matrix included excessive proteolysis of aggrecan core protein and type II collagen, as measured by neo-epitope immunoreactivity. These changes were accompanied by increased expression of metalloproteinase MMP13, type X collagen, cellular hypertrophy and loss of proteoglycan at the articular surface. Using a novel micro-mechanical indentation protocol, it was shown that articular cartilage in the humeral head of 4-month-old Fgfr3(-/-) mice was less resistant to compressive force and less stiff than that of littermate controls. These results identify Fgfr3 signaling as a potential target for intervention in degenerative disorders of cartilage metabolism.

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Citations

Mar 1, 2012·Human Molecular Genetics·Emilie MugnieryLaurence Legeai-Mallet
Oct 20, 2012·Current Opinion in Rheumatology·Richard F Loeser
Apr 26, 2008·Arthritis Research & Therapy·Xin LiHee-Jeong Im
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Jun 16, 2019·Cellular and Molecular Life Sciences : CMLS·Ryota Chijimatsu, Taku Saito

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