title: Age-dependent alteration of TGF-β signalling in osteoarthritis.
abstract: Osteoarthritis (OA) is a disease of articular cartilage, with aging as the main risk factor. In OA, changes in chondrocytes lead to the autolytic destruction of cartilage. Transforming growth factor-β has recently been demonstrated to signal not only via activin receptor-like kinase 5 (ALK5)-induced Smad2/3 phosphorylation, but also via ALK1-induced Smad1/5/8 phosphorylation in articular cartilage. In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the expression of ALK1 is correlated with matrix metalloproteinase-13 expression. The age-dependent shift towards Smad1/5/8 signalling might trigger the differentiation of articular chondrocytes with an autolytic phenotype.
authors.affiliation: Department of Rheumatology, Radboud University Nijmegen Medical Centre Nijmegen, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands. P.vanderkraan@reuma.umcn.nl
authors.forename: Peter M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Blaney Davidson
authors.forename: Peter
authors.initials: P
authors.lastname: ten Dijke
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human