LDHA promotes osteoblast differentiation through histone lactylation

Biochem Biophys Res Commun. 2022 Jul 30:615:31-35. doi: 10.1016/j.bbrc.2022.05.028. Epub 2022 May 13.

Abstract

Osteoblast cells tend to metabolize glucose to lactate via aerobic glycolysis during osteogenic differentiation. However, the function of lactate in this process is still elusive. As a newly discovered protein posttranslational modification, lactate-derived histone lactylation has been found to play important roles in gene regulation and have profound effects on diverse biological processes. Here, we found that the expression of lactate dehydrogenase A (LDHA), intracellular lactate, and histone lactylation levels were all gradually increased during osteogenic differentiation. Knockdown of LDHA impaired the formation of mineralized nodules and ALP activity. RNA-sequencing and subsequent validation experiments showed that JunB expression was decreased in LDHA knockdown cells. Mechanistically, knockdown of LDHA decreased histone lactylation mark enrichment on JunB promoter, and exogenous lactate treatment rescued this effect. Our study revealed a non-canonical function of lactate during osteogenic differentiation.

Keywords: Histone lactylation; LDHA; Lactate; Osteogenic differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Glycolysis / genetics
  • Histones* / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • Lactic Acid / metabolism
  • Osteoblasts / metabolism
  • Osteogenesis*

Substances

  • Histones
  • Isoenzymes
  • Lactic Acid
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5