BCAT1 promotes osteoclast maturation by regulating branched-chain amino acid metabolism

• DOI: 10.1038/s12276-022-00775-3
• Publication Date: 2022-06-27T06:03:12Z
• Authors: Miyeon Go; Eunji Shin; Seo Young Jang; Miso Nam; Geum-Sook Hwang; Soo Young Lee
• Keywords: Bone remodeling

Abstract Branched-chain aminotransferase 1 (BCAT1) transfers the amine group on branched-chain amino acids (BCAAs) to alpha-ketoglutarate. This generates glutamate along with alpha-keto that are eventually oxidized provide cell energy. BCAT1 thus plays a critical role in sustaining BCAA concentrations and availability as an energy source. Osteoclasts have high metabolic needs during differentiation. When we assessed levels of bone marrow macrophages (BMMs) were undergoing receptor activator nuclear factor κB ligand (RANKL)-induced osteoclast differentiation, found steadily increase this process. In vitro analyses then showed all three BCAAs but especially valine needed for maturation. Moreover, selective inhibition gabapentin significantly reduced Expression enzymatically dead also abrogated Importantly, inhibited lipopolysaccharide (LPS)-induced loss calvaria mice. These findings suggest could serve therapeutic target dampens formation.