Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice
article
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
Topics
Collagenase 3Core proteinEpitopeFibroblast growth factor receptor 3ProteoglycanAnimal cellAnimal experimentAnimal modelAnimal tissueCartilage degenerationCartilage matrixCell structureCompressionControlled studyGenetic proceduresHumerus headHypertrophyImmunoreactivityMouseNonhumanPhysical resistanceProtein deficiencyProtein degradationProtein expressionProtein targetingRigiditySignal transductionSynoviumTissue metabolismAggrecansAnimalsArthritisCartilageCartilage DiseasesCartilage, ArticularChondrocytesCollagen Type IICollagen Type XCollagenasesCrosses, GeneticEpitopesExtracellular Matrix ProteinsLectins, C-TypeMatrix Metalloproteinase 13MiceMice, TransgenicOsteoblastsProteochondroitin SulfatesReceptor, Fibroblast Growth Factor, Type 3Signal Transduction
TNO Identifier
239296
ISSN
09646906
Source
Human Molecular Genetics, 15(11), pp. 1783-1792.
Pages
1783-1792
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