title: Chondroitin sulfate N-acetylgalactosaminyltransferase 1 is necessary for normal endochondral ossification and aggrecan metabolism.
abstract: Chondroitin sulfate (CS) is a glycosaminoglycan, consisting of repeating disaccharide units of N-acetylgalactosamine and glucuronic acid residues, and plays important roles in development and homeostasis of organs and tissues. Here, we generated and analyzed mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGalNAcT-1). Csgalnact1(-/-) mice were viable and fertile but exhibited slight dwarfism. Biochemically, the level of CS in Csgalnact1(-/-) cartilage was reduced to ∼50% that of wild-type cartilage, whereas its chain length was similar to wild-type mice, indicating that CSGalNAcT-1 participates in the CS chain initiation as suggested in the previous study (Sakai, K., Kimata, K., Sato, T., Gotoh, M., Narimatsu, H., Shinomiya, K., and Watanabe, H. (2007) J. Biol. Chem. 282, 4152-4161). Histologically, the growth plate of Csgalnact1(-/-) mice contained shorter and slightly disorganized chondrocyte columns with a reduced volume of the extracellular matrix principally in the proliferative layer. Immunohistochemical analysis revealed that the level of both aggrecan and link protein 1 were decreased in Csgalnact1(-/-) cartilage. Western blot analysis demonstrated an increase in processed forms of aggrecan core protein. These results suggest that CSGalNAcT-1 is required for normal levels of CS biosynthesis in cartilage. Our observations suggest that CSGalNAcT-1 is necessary for normal levels of endochondral ossification, and the decrease in CS amount in the growth plate by its absence causes a rapid catabolism of aggrecan.
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Open Space Laboratory Central-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ikehara
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirano
authors.forename: Katsue
authors.initials: K
authors.lastname: Kiyohara
authors.forename: Kozue
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Akira
authors.initials: A
authors.lastname: Togayachi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ema
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Koji
authors.initials: K
authors.lastname: Kimata
authors.forename: Hideto
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002356:Cartilage / Q000201:enzymology* / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D002809:Chondroitin Sulfates / Q000096:biosynthesis* / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D006132:Growth Plate / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D000099249:Proteoglycan Link Protein
chemical_list: D053674:Aggrecans; D002809:Chondroitin Sulfates; D016326:Extracellular Matrix Proteins; D017350:N-Acetylgalactosaminyltransferases; D011509:Proteoglycans; D000099249:Proteoglycan Link Protein; C472559:chondroitin sulfate N-acetylgalactosaminyltransferase-1