Author： Valverde-Franco G. Binette J.S. Li W. Wang H. Chai S. Laflamme F. Tran-Khanh N. Quenneville E. Meijers T. Poole A.R. Mort J.S. Buschmann M.D. Henderson J.E.
Publisher： Oxford University Press
ISSN： 1460-2083
Source： Human Molecular Genetics, Vol.15, Iss.11, 2006-06, pp. : 1783-1792
Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.
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.
Related content
Access to resources
Recommend
By Guenou Hind Kaabeche Karim Mée Sandrine Le Marie Pierre J.
Human Molecular Genetics, Vol. 14, Iss. 11, 2005-06 ,pp. :