| First Author | Valverde-Franco G | Year | 2006 |
| Journal | Hum Mol Genet | Volume | 15 |
| Issue | 11 | Pages | 1783-92 |
| PubMed ID | 16624844 | Mgi Jnum | J:109576 |
| Mgi Id | MGI:3629319 | Doi | 10.1093/hmg/ddl100 |
| Citation | Valverde-Franco G, et al. (2006) Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice. Hum Mol Genet 15(11):1783-92 |
| abstractText | 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. |
