Abstract
Cartilage extracellular matrix (ECM) contains large amounts of proteoglycans made of a protein core decorated by highly sulfated sugar chains, the glycosaminoglycans (GAGs). GAGs desulfation, a necessary step for their degradation, is exerted by sulfatases that are activated by another enzyme, Sulfatase-Modifying Factor 1 (SUMF1), whose inactivation in humans leads to severe skeletal abnormalities. We show here that despite being expressed in both osteoblasts and chondrocytes Sumf1 does not affect osteoblast differentiation. Conversely, in chondrocytes it favors ECM production and autophagy and promotes proliferation and differentiation by limiting FGF signaling. Thus, proteoglycan desulfation is a critical regulator of chondrogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autophagy / physiology*
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Cell Differentiation
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Cell Proliferation
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Chondrocytes / cytology
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Chondrocytes / physiology*
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Extracellular Matrix / metabolism
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Female
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Fibroblast Growth Factors / physiology*
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Growth Plate / cytology
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Growth Plate / embryology
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Growth Plate / metabolism
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Mice
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Mice, Knockout
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Mice, Transgenic
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Osteogenesis*
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Oxidoreductases Acting on Sulfur Group Donors
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Pregnancy
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Proteoglycans / chemistry
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Proteoglycans / metabolism*
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Signal Transduction
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Sulfatases / deficiency
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Sulfatases / genetics
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Sulfatases / metabolism
Substances
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Proteoglycans
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Fibroblast Growth Factors
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Oxidoreductases Acting on Sulfur Group Donors
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Sumf1 protein, mouse
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Sulfatases