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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Activin Receptors, Type II / metabolism
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Aging / physiology*
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Cell Differentiation / physiology
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Chondrocytes / cytology
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Chondrocytes / physiology
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Fibrosis / pathology
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Humans
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Osteoarthritis / pathology
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Osteoarthritis / physiopathology*
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Osteoarthritis / therapy
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Protein Serine-Threonine Kinases / metabolism
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism
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Signal Transduction / physiology*
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Smad Proteins / metabolism
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Synovial Membrane / pathology
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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Receptors, Transforming Growth Factor beta
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Smad Proteins
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Transforming Growth Factor beta
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Protein Serine-Threonine Kinases
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ACVRL1 protein, human
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Activin Receptors, Type II
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Receptor, Transforming Growth Factor-beta Type I
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TGFBR1 protein, human