SLC1A5provides glutamine and asparagine necessary for bone development in mice

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 identifySlc1a5as a critical amino acid transporter during bone development. Using a genetic and metabolomic approach, we showSlc1a5acts cell autonomously in osteoblasts to import glutamine and asparagine. DeletingSlc1a5or reducing either glutamine or asparagine availability prevents protein synthesis and osteoblast differentiation. Mechanistically, glutamine and asparagine metabolism support amino acid biosynthesis. Thus, osteoblasts depend onSlc1a5to provide glutamine and asparagine, which are subsequently used to produce non-essential amino acids and support osteoblast differentiation and bone development.