論文

査読有り 国際誌
2021年8月21日

O‐GlcNAcylation drives calcium signaling toward osteoblast differentiation: A bioinformatics‐oriented study

BioFactors
  • Yao Weng
  • Ziyi Wang
  • Yoko Fukuhara
  • Airi Tanai
  • Mika Ikegame
  • Daisuke Yamada
  • Takeshi Takarada
  • Takashi Izawa
  • Satoru Hayano
  • Kaya Yoshida
  • Hiroshi Kamioka
  • Hirohiko Okamura
  • 全て表示

47
6
開始ページ
992
終了ページ
1015
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/biof.1774
出版者・発行元
Wiley

This study aimed to reveal the possible mechanisms by which O-linked-N-acetylglucosaminylation (O-GlcNAcylation) regulates osteoblast differentiation using a series of bioinformatics-oriented experiments. To examine the influence of O-GlcNAcylation levels on osteoblast differentiation, osteoblastic MC3T3-E1 cells were treated with O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) inhibitors. Correlations between the levels of O-GlcNAcylation and the expression of osteogenic markers as well as OGT were evaluated by qPCR and western blotting. The O-GlcNAcylated proteins assumed to correlate with Runx2 expression were retrieved from several public databases and used for further bioinformatics analysis. Following the findings of the bioinformatics analysis, intracellular calcium ([Ca2+ ]i ) was monitored in the cells treated with OGT and OGA inhibitors using a confocal laser-scanning microscope (CLS). The interaction effect between O-GlcNAcylation and [Ca2+ ]i on osteogenic marker expression was determined using stable OGT knockdown MC3T3-E1 cells. O-GlcNAcylation was positively associated with osteoblast differentiation. The time-course profile of global O-GlcNAcylated proteins showed a distinctive pattern with different molecular weights during osteoblast differentiation. The expression pattern of several O-GlcNAcylated proteins was significantly similar to that of Runx2 expression. Bioinformatic analysis of the retrieved Runx2-related-O-GlcNAcylated-proteins revealed the importance of [Ca2+ ]i . CLS showed that alteration of O-GlcNAcylation rapidly changed [Ca2+ ]i in MC3T3-E1 cells. O-GlcNAcylation and [Ca2+ ]i showed an interaction effect on the expression of osteogenic markers. OGT knockdown disrupted the [Ca2+ ]i -induced expression changes of osteogenic markers. O-GlcNAcylation interacts with [Ca2+ ]i and elicits osteoblast differentiation by regulating the expression of osteogenic markers.

リンク情報
DOI
https://doi.org/10.1002/biof.1774
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34418170
共同研究・競争的資金等の研究課題
顎顔面領域稀少性遺伝子疾患における骨代謝制御機構とその破綻のエピゲノム解析
共同研究・競争的資金等の研究課題
顎顔面領域骨代謝性疾患におけるエピゲノム制御による新規骨リモデリング機構の解明
URL
https://onlinelibrary.wiley.com/doi/pdf/10.1002/biof.1774
URL
https://onlinelibrary.wiley.com/doi/full-xml/10.1002/biof.1774
ID情報
  • DOI : 10.1002/biof.1774
  • ISSN : 0951-6433
  • eISSN : 1872-8081
  • PubMed ID : 34418170

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