SLC1A5 provides glutamine and asparagine necessary for bone development in mice

Abstract Osteoblast differentiation is sequentially characterized by high rates of proliferation followed by increased protein and matrix synthesis, processes that require substantial amino acid acquisition and production. How osteoblasts obtain or maintain intracellular amino acid production is poorly understood. Here we identify Slc1a5 as a critical amino acid transporter during bone development. Using a genetic and metabolomic approach, we show Slc1a5 acts cell autonomously in osteoblasts to import glutamine and asparagine. Deleting Slc1a5 or reducing either glutamine or asparagine availability prevents protein synthesis and osteoblast differentiation. Mechanistically, glutamine and asparagine metabolism support amino acid biosynthesis. Thus, osteoblasts depend on Slc1a5 to provide glutamine and asparagine, which are subsequently used to produce non-essential amino acids and support osteoblast differentiation and bone development.