Proteoglycan desulfation determines the efficiency of chondrocyte autophagy and the extent of FGF signaling during endochondral ossification.
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.
Settembre
Carmine
C
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Arteaga-Solis
Emilio
E
McKee
Marc D
MD
de Pablo
Raquel
R
Al Awqati
Qais
Q
Ballabio
Andrea
A
Karsenty
Gerard
G
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006132:Growth Plate / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010012:Osteogenesis; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011247:Pregnancy; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013429:Sulfatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D011509:Proteoglycans; D005346:Fibroblast Growth Factors; D050862:Oxidoreductases Acting on Sulfur Group Donors; C519507:Sumf1 protein, mouse; D013429:Sulfatases