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Updated: Sep 22, 2025

Differentiation and Characterization of Osteoclasts from Human Induced Pluripotent Stem Cells
Published on: March 22, 2024
LDHA promotes osteoblast differentiation through histone lactylation
Feige Nian1, Yezhou Qian2, Fangyan Xu3
1Department of Rheumatology and Immunology, The Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, Zhejiang, 314033, China.
Lactate dehydrogenase A (LDHA) is crucial for osteogenic differentiation by promoting histone lactylation on the JunB promoter, revealing lactate's non-canonical role in bone formation.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Osteoblast cells utilize aerobic glycolysis, converting glucose to lactate during osteogenic differentiation.
- The precise function of lactate in this process remains unclear.
- Histone lactylation, a post-translational modification, influences gene regulation and biological processes.
Purpose of the Study:
- To investigate the role of lactate dehydrogenase A (LDHA) and lactate in osteogenic differentiation.
- To elucidate the mechanism by which LDHA affects gene expression during bone formation.
Main Methods:
- Measuring lactate dehydrogenase A (LDHA), intracellular lactate, and histone lactylation levels during osteogenic differentiation.
- Utilizing LDHA knockdown and RNA-sequencing to assess effects on osteogenic differentiation and gene expression.
- Analyzing histone lactylation enrichment on the JunB promoter.
Main Results:
- LDHA expression, intracellular lactate, and histone lactylation increased during osteogenic differentiation.
- LDHA knockdown inhibited mineralized nodule formation and alkaline phosphatase (ALP) activity.
- LDHA knockdown led to decreased JunB expression, linked to reduced histone lactylation on its promoter.
Conclusions:
- LDHA plays a critical role in osteogenic differentiation through lactate production and histone lactylation.
- Histone lactylation on the JunB promoter is a key mechanism mediating LDHA's function.
- This study uncovers a novel, non-canonical role for lactate in osteogenic differentiation.
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