Elucidation of the role of metabolic reprogramming in osteoclast differentiation

Osteoclasts dramatically alter their metabolic activity during cell differentiation. This change in the metabolic status is termed'metabolic reprogramming',but its role in osteoclast is not fully understood. Using metabolomics approach, we found that metabolic reprogramming during osteoclast differentiation increased intracellular S-adenosyle methionine (SAM), a metabolite of the methionine cycle. SAM is the universal methyl donor for methylation reactions, including histone and DNA methylation. Furthermore, SAM-mediated DNA methylation is required for osteoclast differentiation. These findings reveal the novel role of SAM metabolism in regulating osteoclast differentiation.