Proteoglycan desulfation determines the efficiency of chondrocyte autophagy and the extent of FGF signaling during endochondral ossification

C Settembre, E Arteaga-Solis, MD McKee… - Genes & …, 2008 - genesdev.cshlp.org
C Settembre, E Arteaga-Solis, MD McKee, R de Pablo, Q Al Awqati, A Ballabio, G Karsenty
Genes & development, 2008genesdev.cshlp.org
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 …
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.
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