title: Global increase in O-linked N-acetylglucosamine modification promotes osteoblast differentiation.
abstract: The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts, and an imbalance in this bone metabolism leads to osteoporosis. Here, we found that osteoblast differentiation in MC3T3-E1 cells is promoted by the inactivation of O-linked β-N-acetylglucosaminidase (O-GlcNAcase) and suppressed by the inactivation of O-GlcNAc transferase, as indicated by extracellular matrix calcification. The expression of osteogenic genes such as alp, ocn, and bsp during osteoblast differentiation was positively regulated in a O-GlcNAc glycosylation-dependent manner. Because it was confirmed that Ets1 and Runx2 are the two key transcription factors responsible for the expression of these osteogenic genes, their transcriptional activity might therefore be regulated by O-GlcNAc glycosylation. However, osteoclast differentiation of RAW264 cells, as indicated by the expression and activity of tartrate-resistant acid phosphatase, was unaffected by the inactivation of either O-GlcNAcase or O-GlcNAc transferase. Our findings suggest that an approach to manipulate O-GlcNAc glycosylation could be useful for developing the therapeutics for osteoporosis.
authors: Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
authors: Takahiro
authors: T
authors: Koyama
authors: Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan. Electronic address: k_kamemura@nagahama-i-bio.ac.jp.
authors: Kazuo
authors: K
authors: Kamemura
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D002113:Calcification, Physiologic / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D006031:Glycosylation; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism* / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C494042:Ets1 protein, mouse; D007527:Isoenzymes; D050784:Proto-Oncogene Protein c-ets-1; C493716:Runx2 protein, mouse; D014157:Transcription Factors; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases
keywords: MC3T3-E1; O-GlcNAc glycosylation; Osteoblast differentiation; Osteoclast differentiation; RAW264