論文

国際誌
2023年

Lactate-induced histone lactylation by p300 promotes osteoblast differentiation.

PloS one
  • Erika Minami
  • ,
  • Kiyohito Sasa
  • ,
  • Atsushi Yamada
  • ,
  • Ryota Kawai
  • ,
  • Hiroshi Yoshida
  • ,
  • Haruhisa Nakano
  • ,
  • Koutaro Maki
  • ,
  • Ryutaro Kamijo

18
12
開始ページ
e0293676
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0293676

Lactate, which is synthesized as an end product by lactate dehydrogenase A (LDHA) from pyruvate during anaerobic glycolysis, has attracted attention for its energy metabolism and oxidant effects. A novel histone modification-mediated gene regulation mechanism termed lactylation by lactate was recently discovered. The present study examined the involvement of histone lactylation in undifferentiated cells that underwent differentiation into osteoblasts. C2C12 cells cultured in medium with a high glucose content (4500 mg/L) showed increases in marker genes (Runx2, Sp7, Tnap) indicating BMP-2-induced osteoblast differentiation and ALP staining activity, as well as histone lactylation as compared to those cultured in medium with a low glucose content (900 mg/L). Furthermore, C2C12 cells stimulated with the LDH inhibitor oxamate had reduced levels of BMP-2-induced osteoblast differentiation and histone lactylation, while addition of lactate to C2C12 cells cultured in low glucose medium resulted in partial restoration of osteoblast differentiation and histone lactylation. These results indicate that lactate synthesized by LDHA during glucose metabolism is important for osteoblast differentiation of C2C12 cells induced by BMP-2. Additionally, silencing of p300, a possible modifier of histone lactylation, also inhibited osteoblast differentiation and reduced histone lactylation. Together, these findings suggest a role of histone lactylation in promotion of undifferentiated cells to undergo differentiation into osteoblasts.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0293676
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/38051708
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697613
ID情報
  • DOI : 10.1371/journal.pone.0293676
  • PubMed ID : 38051708
  • PubMed Central 記事ID : PMC10697613

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