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 to regulate protein synthesis and osteoblast differentiation. SLC1A5 provides both glutamine and asparagine which are essential for osteoblast differentiation. Mechanistically, glutamine and to a lesser extent asparagine 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.
All data generated or analyzed during this study are included in the manuscript.
- Courtney M Karner
- Courtney M Karner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal procedures were approved (APN 2020-102999) by the Animal Studies Committees at Duke University and the University of Texas Southwestern Medical Center at Dallas.
- Ernestina Schipani, University of Pennsylvania, United States
- Received: June 24, 2021
- Accepted: October 12, 2021
- Accepted Manuscript published: October 14, 2021 (version 1)
© 2021, Sharma et al.
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