Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
Elife. 2021 Oct 14;10:e71595. doi: 10.7554/eLife.71595.
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 to provide glutamine and asparagine, which are subsequently used to produce non-essential amino acids and support osteoblast differentiation and bone development.
成骨细胞分化的特征是增殖率高，随后蛋白和基质合成增加，这些过程需要大量的氨基酸获取和产生。然而，成骨细胞如何获得或维持细胞内氨基酸的产生还知之甚少。在这里，我们鉴定出 SLC1A5 是骨发育过程中关键的氨基酸转运蛋白。通过遗传和代谢组学方法，我们发现 SLC1A5 能够自主调节蛋白合成和成骨细胞分化。SLC1A5 提供谷氨酰胺和天冬酰胺，这对于成骨细胞分化是必不可少的。从机制上讲，谷氨酰胺，在较小程度上天冬酰胺，支持氨基酸的生物合成。因此，成骨细胞依赖 SLC1A5 来提供谷氨酰胺和天冬酰胺，随后这些氨基酸被用于产生非必需氨基酸，并支持成骨细胞分化和骨发育。
