Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice
Open Access
- 19 April 2006
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 15 (11), 1783-1792
- https://doi.org/10.1093/hmg/ddl100
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.Keywords
This publication has 24 references indexed in Scilit:
- Promotion of the intrinsic damage–repair response in articular cartilage by fibroblastic growth factor-2Osteoarthritis and Cartilage, 2005
- Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stromaCell and tissue research, 2005
- Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacityOsteoarthritis and Cartilage, 2004
- Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantationThe Journal of Gene Medicine, 2004
- Developmental regulation of the growth plateNature, 2003
- Articular cartilage repair: basic science and clinical progress. A review of the current status and prospectsOsteoarthritis and Cartilage, 2002
- Inactivation of one allele of the type II collagen gene alters the collagen network in murine articular cartilage and makes cartilage softerAnnals Of The Rheumatic Diseases, 2001
- Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in miceJCI Insight, 2001
- Endochondral bone formation and development in the axial and appendicular skeletonPublished by Cambridge University Press (CUP) ,2000
- Collagen type I antisense and collagen type IIA messenger RNA is expressed in adult murine articular cartilageOsteoarthritis and Cartilage, 1998