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

Carmine Settembre; Emilio Arteaga-Solis; Marc D. McKee; Raquel de Pablo; Qais Al Awqati; Andrea Ballabio; Gerard Karsenty

doi:10.1101/gad.1711308

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

¹ Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA;
² Telethon Institute of Genetic and Medicine (TIGEM), Naples 80131, Italy;
³ Faculty of Dentistry, and Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec H3A 2B2, Canada;
⁴ Medical Genetics, Department of Pediatrics, Federico II University, Naples 80131, Italy

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.

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Footnotes

⁵
↵5 Corresponding author.

↵5 E-MAIL gk2172{at}columbia.edu; FAX (212) 923-2090.
Supplemental material is available at http://www.genesdev.org.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1711308.
- Received June 28, 2008.
- Accepted August 11, 2008.