Abstract
Skeleton has emerged as an endocrine organ which is both capable of regulating energy metabolism and being a target for it. Glutamine is the most bountiful and flexible amino acid in the body which provides adenosine 5′-triphosphate (ATP) demands for cells. Emerging evidences support that glutamine which acts as the second metabolic regulator after glucose exerts crucial roles in bone homeostasis at cellular level, including the lineage allocation and proliferation of bone mesenchymal stem cells (BMSCs), the matrix mineralization of osteoblasts, and the biosynthesis in chondrocytes. The integrated mechanism consisting of WNT, mammalian target of rapamycin (mTOR), and reactive oxygen species (ROS) signaling pathway in a glutamine-dependent pattern is responsible to regulate the complex intrinsic biological process, despite more extensive molecules are deserved to be elucidated in glutamine metabolism further. Indeed, dysfunctional glutamine metabolism enhances the development of degenerative bone diseases, such as osteoporosis and osteoarthritis, and glutamine or glutamine progenitor supplementation can partially restore bone defects which may promote treatment of bone diseases, although the mechanisms are not quite clear. In this review, we will summarize and update the latest research findings and clinical trials on the crucial regulatory roles of glutamine metabolism in BMSCs and BMSC-derived bone cells, also followed with the osteoclasts which are important in bone resorption.
Highlights
Bone is a relatively dynamic organ which provides stiffness, shape, support, and locomotion for body structures [1]
We reviewed and updated the crucial regulatory roles of glutamine metabolism in bone mesenchymal stem cells (BMSCs), BMSC-derived bone cells, and osteoclasts which expected to provide a novel therapeutic perspective for bone destructive disorders
Recent evidences indicated that glutamine is a critical regulator in bone homeostasis via supporting energy as a substitute carbon source through TCA cycle and providing precursors for protein and nucleic acid synthesis
Summary
Bone is a relatively dynamic organ which provides stiffness, shape, support, and locomotion for body structures [1] It undergoes modeling and constant remodeling throughout life, exhibiting structure and shape changes. Osteoblasts for bone formation and osteoclasts for bone resorption are the main cells involved in bone remodeling; osteocytes derived from osteoprogenitors are crucial in this biological process [3,4,5,6]. The fuel sources containing glucose, free fatty acids, and the amino acids are excellent substrates for generating ATP in both cytoplasm and mitochondria through oxidative phosphorylation [9,10,11] Their consumption and catabolism are adjusted automatically in order to match the distinctive energy demands in different stages covering proliferation, differentiation, and apoptosis, in which intracellular signaling molecules serve as checkpoints. We reviewed and updated the crucial regulatory roles of glutamine metabolism in BMSCs, BMSC-derived bone cells, and osteoclasts which expected to provide a novel therapeutic perspective for bone destructive disorders
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