Title
Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice
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.
TNO Kwaliteit van Leven
Publication year
2006
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 Ffr3-/- 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. © 2006 Oxford University Press. Chemicals / CAS: collagenase 3, 175449-82-8; fibroblast growth factor receptor 3, 306781-00-0; Agc1 protein, mouse; Aggrecans; Collagen Type II; Collagen Type X; Collagenases, EC 3.4.24.-; Epitopes; Extracellular Matrix Proteins; Lectins, C-Type; Matrix Metalloproteinase 13, EC 3.4.24.-; Mmp13 protein, mouse, EC 3.4.24.-; Proteochondroitin Sulfates; Receptor, Fibroblast Growth Factor, Type 3, EC 2.7.1.112
Subject
Collagenase 3
Core protein
Epitope
Fibroblast growth factor receptor 3
Proteoglycan
Animal cell
Animal experiment
Animal model
Animal tissue
Cartilage degeneration
Cartilage matrix
Cell structure
Compression
Controlled study
Genetic procedures
Humerus head
Hypertrophy
Immunoreactivity
Mouse
Nonhuman
Physical resistance
Protein deficiency
Protein degradation
Protein expression
Protein targeting
Rigidity
Signal transduction
Synovium
Tissue metabolism
Aggrecans
Animals
Arthritis
Cartilage
Cartilage Diseases
Cartilage, Articular
Chondrocytes
Collagen Type II
Collagen Type X
Collagenases
Crosses, Genetic
Epitopes
Extracellular Matrix Proteins
Lectins, C-Type
Matrix Metalloproteinase 13
Mice
Mice, Transgenic
Osteoblasts
Proteochondroitin Sulfates
Receptor, Fibroblast Growth Factor, Type 3
Signal Transduction
To reference this document use:
http://resolver.tudelft.nl/uuid:10812a66-5082-46a1-8b5b-324903ddd05f
DOI
https://doi.org/10.1093/hmg/ddl100
TNO identifier
239296
ISSN
0964-6906
Source
Human Molecular Genetics, 15 (11), 1783-1792
Document type
article