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Overexpression of Galnt3 in Chondrocytes Resulted in Dwarfism Due to the Increase of Mucin-type O-Glycans and Reduction of Glycosaminoglycans

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Title: Overexpression of Galnt3 in Chondrocytes Resulted in Dwarfism Due to the Increase of Mucin-type O-Glycans and Reduction of Glycosaminoglycans
Authors: Yoshida, Carolina Andrea Browse this author
Kawane, Tetsuya Browse this author
Moriishi, Takeshi Browse this author
Purushothaman, Anurag Browse this author
Miyazaki, Toshihiro Browse this author
Komori, Hisato Browse this author
Mori, Masako Browse this author
Qin, Xin Browse this author
Hashimoto, Ayako Browse this author
Sugahara, Kazuyuki Browse this author →KAKEN DB
Yamana, Kei Browse this author
Takada, Kenji Browse this author
Komori, Toshihisa Browse this author
Keywords: Chondrocyte
Glycosaminoglycan
Glycosyltransferase
Mucin
Proteoglycan
Aggrecan
Galnt3
Mucin-type O-Glycan
Issue Date: 19-Sep-2014
Publisher: American Society for Biochemistry and Molecular Biology (ASBMB)
Journal Title: Journal of Biological Chemistry
Volume: 289
Issue: 38
Start Page: 26584
End Page: 26596
Publisher DOI: 10.1074/jbc.M114.555987
PMID: 25107907
Abstract: Galnt3, UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3, transfers N-acetyl-d-galactosamine to serine and threonine residues, initiating mucin type O-glycosylation of proteins. We searched the target genes of Runx2, which is an essential transcription factor for chondrocyte maturation, in chondrocytes and found that Galnt3 expression was up-regulated by Runx2 and severely reduced in Runx2−/− cartilaginous skeletons. To investigate the function of Galnt3 in chondrocytes, we generated Galnt3−/− mice and chondrocyte-specific Galnt3 transgenic mice under the control of the Col2a1 promoter-enhancer. Galnt3−/− mice showed a delay in endochondral ossification and shortened limbs at embryonic day 16.5, suggesting that Galnt3 is involved in chondrocyte maturation. Galnt3 transgenic mice presented dwarfism, the chondrocyte maturation was retarded, the cell cycle in chondrocytes was accelerated, premature chondrocyte apoptosis occurred, and the growth plates were disorganized. The binding of Vicia villosa agglutinin, which recognizes the Tn antigen (GalNAc-O-Ser/Thr), was drastically increased in chondrocytes, and aggrecan (Acan) was highly enriched with Tn antigen. However, safranin O staining, which recognizes glycosaminoglycans (GAGs), and Acan were severely reduced. Chondroitin sulfate was reduced in amount, but the elongation of chondroitin sulfate chains had not been severely disturbed in the isolated GAGs. These findings indicate that overexpression of Galnt3 in chondrocytes caused dwarfism due to the increase of mucin-type O-glycans and the reduction of GAGs, probably through competition with xylosyltransferases, which initiate GAG chains by attaching O-linked xylose to serine residues, suggesting a negative effect of Galnt family proteins on Acan deposition in addition to the positive effect of Galnt3 on chondrocyte maturation.
Rights: This research was originally published in Journal of Biological Chemistry. Carolina Andrea Yoshida, Tetsuya Kawane, Takeshi Moriishi, Anurag Purushothaman, Toshihiro Miyazaki, Hisato Komori, Masako Mori, Xin Qin, Ayako Hashimoto, Kazuyuki Sugahara, Kei Yamana, Kenji Takada and Toshihisa Komori. Overexpression of Galnt3 in Chondrocytes Resulted in Dwarfism Due to the Increase of Mucin-type O-Glycans and Reduction of Glycosaminoglycans. Journal of Biological Chemistry. 2014; Vol:289(38) p26584-26596. © the American Society for Biochemistry and Molecular Biology
Type: article
URI: http://hdl.handle.net/2115/62911
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 菅原 一幸

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