LDHA promotes osteoblast differentiation through histone lactylation

• Published in: Biochemical and biophysical research communications 2022-07, Vol.615, p.31-35
• Main Authors: Nian, Feige, Qian, Yezhou, Xu, Fangyan, Yang, Mingfeng, Wang, Hongzhi, Zhang, Zhufeng
• Format: Article
• Language: English
• Subjects: Histone lactylation; Lactate; LDHA; Osteogenic differentiation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.05.028

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. •LDHA and histone lactylation H3K18lac mark are gradually increased during osteogenic differentiation.•Manipulation of LDHA expression affects osteogenic differentiation.•The osteogenic differentiation pathway is enriched in LDHA knockdown osteoblast cells.•LDHA regulates JunB expression and osteogenic differentiation through H3K18lac mark.