Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells
Open accessAbstract
Skeletal stem cells (SSCs) are postulated to provide a continuous supply of osteoblasts throughout life. However, under certain conditions, the SSC population can become incorrectly specified or is not maintained, resulting in reduced osteoblast formation, decreased bone mass, and in severe cases, osteoporosis. Glutamine metabolism has emerged as a critical regulator of many cellular processes in diverse pathologies. The enzyme glutaminase (GLS) deaminates glutamine to form glutamate-the rate-limiting first step in glutamine metabolism. Using genetic and metabolic approaches, we demonstrate GLS and glutamine metabolism are required in SSCs to regulate osteoblast and adipocyte specification and bone formation. Mechanistically, transaminase-dependent α-ketoglutarate production is critical for the proliferation, specification, and differentiation of SSCs. Collectively, these data suggest stimulating GLS activity may provide a therapeutic approach to expand SSCs in aged individuals and enhance osteoblast differentiation and activity to increase bone mass.
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When osteoblasts are induced to undergo mineralization, glucose alone is inadequate to fulfill their energy needs; the degree of mineralization only increases when cells are provided with glucose and glutamine supplementation.
“It has been observed that when osteoblasts are induced to undergo mineralization, glucose alone is inadequate to fulfill their energy needs. The degree of mineralization only increases when cells are provided with glucose and glutamine supplementation [64, 65].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [65]
The Results section reports that withdrawing glutamine during skeletal stem cell differentiation reduced matrix mineralization, supporting the claim that glutamine availability matters. But the Discussion says glutamine did not appear to be a major energy source and that inhibiting its metabolism did not cause energetic stress; it does not support the assertion that glucose alone fails to meet the cells’ energy needs. The experiment also concerned skeletal stem cells differentiating into osteoblasts, rather than supplementation of already differentiated osteoblasts. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn skeletal stem cells, GLS and glutamine metabolism are required for regulation of osteoblast and adipocyte specification and physiological bone formation.
“In skeletal stem cells (SSCs), GLS and glutamine metabolism are required for the regulation of osteoblast and adipocyte specification and physiological bone formation107.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [107]
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“Glutaminase Promotes BMSCs differentiated toward osteoblasts Increases a-ketoglutarate production [49] Ketoglutaric acid Promotes osteogenic potential of BMSCs Decreases histone methylations accumulations [52] Kynurenine Inhibits osteogenic differentiation in BMSCs and hMSCs Upregulates miR-493-5b while downregulates…”
BackgroundInfluentialMetabolic Regulation of Cell Fate and Function
Ghosh-Choudhary, S. K., Liu, J., & Finkel, T. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.12.005 · Cited by 106 · see citing works
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Dual Effects of Lipid Metabolism on Osteoblast Function
Alekos, N. S., Moorer, M. C., & Riddle, R. C. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.578194 · Cited by 97 · see citing works
“Cells of the osteoblast lineage also consume a significant amount of glutamine which is required for skeletal stem cell specification, can be catabolized by the tricarboxylic acid cycle to generate ATP, and serves as a regulatory signal to maintain endoplasmic reticulum health during stages of heightened protein synth…”
BackgroundImmunomodulatory properties of mesenchymal stromal/stem cells: The link with metabolism
Li, H., Dai, H., & Li, J. (2022) · Journal of Advanced Research · doi:10.1016/j.jare.2022.05.012 · Cited by 94 · see citing works
“Stimulation of the enzyme glutaminase (Gls), which broke down glutamine to form glutamate and a-KG, enhanced BMSC osteogenesis whereas diminished adipogenesis [105].”
BackgroundThe role of microRNAs in bone development
Bell‐Hensley, A., & McAlinden, A. (2020) · Bone · doi:10.1016/j.bone.2020.115760 · Cited by 89 · see citing works
“This work is in agreement with a recent report showing a positive role for glutaminase in regulating osteoblast differentiation [132].”
ResultThe paradox of metabolism in quiescent stem cells
Coller, H. A. (2019) · FEBS Letters · doi:10.1002/1873-3468.13608 · Cited by 81 · see citing works
The role of autophagy in bone homeostasis
Guo, Y., Su, T., Yang, M., Li, C., Guo, Q., Xiao, Y., Huang, Y., Liu, Y., & Luo, X. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30111 · Cited by 79 · see citing works
“Degenerative changes from BMMSCs include unbalanced differentiation and reduced proliferation during aging (Yu et al., 2019).”
BackgroundZhang, Y., Huang, Z., Han, W., Wu, J., Li, S., Qin, T., Zhang, C., Shi, M., Han, S., Gao, B., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06000-3 · Cited by 80 · see citing works
Na, J., Yang, Z., Shi, Q., Li, C., Liu, Y., Song, Y., Li, X., Zheng, L., & Fan, Y. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.02.003 · Cited by 79 · see citing works
“Glutamine metabolism has been reported to be critical for stem cell fate specification, even though its contribution to the energy supply is less significant [28,45].”
BackgroundEnergy Metabolism During Osteogenic Differentiation: The Role of Akt
Smith, C. O., & Eliseev, R. A. (2020) · Stem Cells and Development · doi:10.1089/scd.2020.0141 · Cited by 77 · see citing works
“Glutamine is converted to a-ketoglutarate to enter the Krebs cycle through the process of glutaminolysis and is used by OBs as an alternate fuel source [19].”
BackgroundRoles and mechanisms of copper homeostasis and cuproptosis in osteoarticular diseases
Han, J., Luo, J., Wang, C., Капилевич, Л. В., & Zhang, X. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116570 · Cited by 75 · see citing works
Osteometabolism: Metabolic Alterations in Bone Pathologies
Srivastava, R. K., Sapra, L., & Mishra, P. K. (2022) · Cells · doi:10.3390/cells11233943 · Cited by 72 · see citing works
Long, J. T., Leinroth, A. P., Liao, Y., Ren, Y., Mirando, A. J., Nguyen, T., Guo, W., Sharma, D., Rouse, D., Wu, C., et al. (2022) · eLife · doi:10.7554/elife.76932 · Cited by 67 · see citing works
Self-citationBiphasic regulation of osteoblast development via the ERK MAPK–mTOR pathway
Kim, J., Yang, Y.-S., Hong, J., Chaugule, S. R., Chun, H., van der Meulen, M. C. H., Xu, R., Greenblatt, M. B., & Shim, J. (2022) · eLife · doi:10.7554/elife.78069 · Cited by 69 · see citing works
The Role of Bone-Derived Exosomes in Regulating Skeletal Metabolism and Extraosseous Diseases
Lyu, H., Xiao, Y., Guo, Q., Huang, Y., & Luo, X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00089 · Cited by 65 · see citing works
“…gradient ultracentrifugation (van der Pol et al., 2012), size based filtration, size-exclusion chromatography (Rood et al., 2010), immunoaffinity isolation (Kang et al., 2017), precipitation (Coumans et al., 2017; Li P. et al., 2017), fieldflow fractionation (Zhang and Lyden, 2019), and so on.”
MethodStegen, S., Devignes, C.-S., Torrekens, S., Looveren, R. V., Carmeliet, P., & Carmeliet, G. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4219 · Cited by 64 · see citing works
“Eight-week-old male mice were injected with either 80 μg/kg PTH (human PTH [1-34], Bachem AG) or vehicle control (0.”
MethodBioenergetic Metabolism In Osteoblast Differentiation
Shen, L., Hu, G., & Karner, C. M. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00721-2 · Cited by 62 · see citing works
Self-citationGlutathione limits RUNX2 oxidation and degradation to regulate bone formation
Hu, G., Yu, Y., Sharma, D., Pruett‐Miller, S. M., Ren, Y., Zhang, G., & Karner, C. M. (2023) · JCI Insight · doi:10.1172/jci.insight.166888 · Cited by 63 · see citing works
“…studies, including our own, have attributed many of the cellular effects of GLS KO to different metabolites; glutamine-derived α -KG regulates proliferation in skeletal stem cells, and gluta-mine-derived amino acids promote protein and bone matrix synthesis in pre-osteoblasts (19, 20, 46, 47).”
BackgroundSelf-citationBiphasic regulation of glutamine consumption by WNT during osteoblast differentiation
Shen, L., Sharma, D., Yu, Y., Long, F., & Karner, C. (2020) · Journal of Cell Science · doi:10.1242/jcs.251645 · Cited by 61 · see citing works
Self-citationThe bidirectional relationship between metabolism and cell cycle control
Diehl, F. F., Sapp, K. M., & Heiden, M. G. V. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.05.012 · Cited by 58 · see citing works
Zhou, T., Yang, Y., Chen, Q., & Xie, L. (2019) · Stem Cells International · doi:10.1155/2019/8928934 · Cited by 73 · see citing works
“Moreover, another study reported that increased glutathione content from glutamine was important to offset the detrimental effect of ROS to the osteoblast fate [17].”
BackgroundInfluentialHuang, M., Zhao, J., Xu, J., Li, J., Zhuang, Y., & Zhang, X. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.08.027 · Cited by 56 · see citing works
“Meanwhile, metabolic ability also affects the function of stem cells.(44,45) Furthermore, differences between constant and intermittent hormonal stimulation affect the differentiation ability of stem cells.”
BackgroundRole of Essential Amino Acids in Age-Induced Bone Loss
Lv, Z., Shi, W., & Zhang, Q. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911281 · Cited by 56 · see citing works
“demonstrated that in differentiated mineralized skeletal stem cells (SSCs), glutamine’s contribution to citrate (M + 4 and M + 5) was reduced compared with undifferentiated SSCs, which means glutamine contributes more during the differentiation procedure, but is not the major energetic substrate in osteoblasts [26].”
BackgroundBone Marrow Adipocytes: A Critical Player in the Bone Marrow Microenvironment
Wang, L., Zhang, H., Wang, S., Chen, X., & Su, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.770705 · Cited by 55 · see citing works
“Thus, regulating the lineage allocation of BMSCs is an effective way to enhance osteoblastogenesis (Suresh et al., 2019; Yu et al., 2019).”
BackgroundSelf-citationBone marrow adipose tissue: Role in bone remodeling and energy metabolism
Tencerová, M., Ferenčáková, M., & Kassem, M. S. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101545 · Cited by 53 · see citing works
Amino acid metabolism in skeletal cells
Devignes, C.-S., Carmeliet, G., & Stegen, S. (2022) · Bone Reports · doi:10.1016/j.bonr.2022.101620 · Cited by 53 · see citing works
“in SSPC proliferation and bone formation, and is associated with increased marrow adiposity (Yu et al., 2019).”
BackgroundHuang, X., Lan, Y., Shen, J., Zhao, X., Zhou, Y., Wu, W., Mao, J., Wu, Y., Xie, Z., & Chen, Z. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.02.005 · Cited by 56 · see citing works
Ophiopogonin D promotes bone regeneration by stimulating CD31hiEMCNhi vessel formation
Yang, M., Li, C., Xiao, Y., Guo, Q., Huang, Y. H., Su, T., Luo, X., & Jiang, T. (2020) · Cell Proliferation · doi:10.1111/cpr.12784 · Cited by 52 · see citing works
Amino acid metabolism and autophagy in skeletal development and homeostasis
Suzuki, A., & Iwata, J. (2021) · Bone · doi:10.1016/j.bone.2021.115881 · Cited by 54 · see citing works
Neural stem cell metabolism revisited: a critical role for mitochondria.
Scandella, V., Petrelli, F., Moore, D. L., Braun, S., & Knobloch, M. (2023) · Trends in endocrinology and metabolism · doi:10.1016/j.tem.2023.05.008 · Cited by 45 · see citing works
“Several recent studies demonstrated that mitochondrial oxidation of fatty acids, glutamine, and glucose-derived pyruvate is necessary to control the quiescent state in different stem cell types [55,56,71,101,103,104].”
BackgroundSLC1A5 provides glutamine and asparagine necessary for bone development in mice
Sharma, D., Yu, Y., Shen, L., Zhang, G., & Karner, C. M. (2021) · eLife · doi:10.7554/elife.71595 · Cited by 51 · see citing works
Self-citationTumor metabolic reprogramming in lung cancer progression (Review)
Li, X., Liu, M., Liu, H., & Chen, J. (2022) · Oncology Letters · doi:10.3892/ol.2022.13407 · Cited by 52 · see citing works
“GLS is the starting and rate‐limiting enzyme for glutamine catabolism (54); it can be divided into renal GLS1 and hepatic GLS2.”
BackgroundThree-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation
Fang, Q., Zhang, Y., Chen, X., Li, H., Cheng, L., Zhu, W., Zhang, Z., Tang, M., Liu, W., Wang, H., et al. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00436 · Cited by 48 · see citing works
“Proliferation of skeletal stem cells can be regulated through glutamine metabolism (Yu et al., 2019), and the proliferation of intestinal stem cells can be regulated by mitochondrial pyruvate metabolism (Schell et al.”
BackgroundStem Cell Metabolism: Powering Cell-Based Therapeutics
Rigaud, V. O. C., Hoy, R. C., Mohsin, S., & Khan, M. (2020) · Cells · doi:10.3390/cells9112490 · Cited by 47 · see citing works
“Similar to CPCs, many other proliferating cells, such as MSCs [64], utilize glutamine as a source for biosynthesis.”
BackgroundInfluentialShen, L., Yu, Y., Zhou, Y., Pruett-Miller, S. M., Zhang, G.-F., & Karner, C. M. (2022) · eLife · doi:10.7554/elife.76963 · Cited by 48 · see citing works
Self-citationCell energy metabolism and bone formation
Sautchuk, R., & Eliseev, R. A. (2022) · Bone Reports · doi:10.1016/j.bonr.2022.101594 · Cited by 49 · see citing works
“8 is now a consensus that undifferentiated osteoprogenitors prefer glycolysis and show very low OxPhos activity (Shum et al., 2016a; Yu et al., 2019; Smith and Eliseev, 2021; Shares et al., 2018; Chen et al., 2008).”
BackgroundLin, C., Yang, Q., Guo, D., Xie, J., Yang, Y.-S., Chaugule, S. R., DeSouza, N. H., Oh, W., Li, R., Chen, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34694-8 · Cited by 47 · see citing works
“Of note, since amino-acid-transaminase-derived α KG is the critical downstream glutamine metabolite regulating proliferation of skeletal progenitors 29 , cell proliferation rates were largely not altered in Ecsi Prx1 skeletal progenitors with normal glutamine metabolism.”
InfluentialMulati, M., Kobayashi, Y., Takahashi, A., Numata, H., Saito, M., Hiraoka, Y., Ochi, H., Sato, S., Ezura, Y., Yuasa, M., et al. (2019) · Bone · doi:10.1016/j.bone.2019.115076 · Cited by 47 · see citing works
Ezhilarasan, D. (2021) · Hepatobiliary & Pancreatic Diseases International · doi:10.1016/j.hbpd.2021.04.010 · Cited by 39 · see citing works
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“Moreover, in murine models, bone mass formation is sustained by Gln metabolism [16], the inhibition of which also decreases OB differentiation of human mesenchymal stromal cells (MSCs) [17].”
Spontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters
Parker, S. J., Encarnación-Rosado, J., Hollinshead, K. E. R., Hollinshead, D. M., Ash, L. J., Rossi, J. A. K., Lin, E. Y., Sohn, A. S. W., Philips, M. R., Jones, D. R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25228-9 · Cited by 42 · see citing works
Li, X., Liang, T., Dai, B., Chang, L., Zhang, Y., Hu, S., Guo, J., Xu, S., Zheng, L., Yao, H., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci166795 · Cited by 41 · see citing works
Glutamine Metabolism Is Required for Alveolar Regeneration during Lung Injury
Wang, S., Li, X., Ma, Q., Wang, Q., Wu, J., Yu, H., Li, K., Li, Y., Wang, J., Zhang, Q., et al. (2022) · Biomolecules · doi:10.3390/biom12050728 · Cited by 40 · see citing works
Cuproptosis-a potential target for the treatment of osteoporosis
Li, D., Gao, Z., Li, Q., Liu, X., & Liu, H. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1135181 · Cited by 40 · see citing works
“Knockdown of micRO-RNA-200a-3p can promote osteogenic differentiation of BMSCs; GLS overexpression similarly reversed the inhibitory effect of micRO-RNA-200a-3p on osteogenic differentiation (71). miR-206 can directly bind to the 3’-UTR region of GLS mRNA, thereby inhibiting GLS expression and glutamine metabolism; re…”
BackgroundMethodInfluentialSystems Immunology Approaches to Metabolism
Mogilenko, D. A., Sergushichev, A., & Artyomov, M. N. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101220-031513 · Cited by 41 · see citing works
Oxidative phosphorylation in bone cells
Sabini, E., Arboit, L., Khan, M. P., Lanzolla, G., & Schipani, E. (2023) · Bone Reports · doi:10.1016/j.bonr.2023.101688 · Cited by 40 · see citing works
“Conditional deletion of glutaminase in Prx-1(+) skeletal progenitors impairs osteoblast specification, differentiation, and bone formation (Yu et al., 2019).”
BackgroundLee, S.-Y., Kim, H. S., Kim, M. J., Min, K. Y., Choi, W. S., & You, J. S. (2020) · Bone · doi:10.1016/j.bone.2020.115836 · Cited by 39 · see citing works
The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis
Li, Z., Yue, M., Liu, X., Liu, Y., Lv, L., Zhang, P., & Zhou, Y. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.03.036 · Cited by 39 · see citing works
“It has been reported that glutamine could promote osteogenic differentiation of BMMSCs via providing ATP through TCA cycle to meet energetic and synthetic demands [44].”
BackgroundEnergy Metabolism of Osteocytes
Karthik, V., & Guntur, A. R. (2021) · Current Osteoporosis Reports · doi:10.1007/s11914-021-00688-6 · Cited by 36 · see citing works
Park, K., Park, J.-I., Lee, S., Yoo, K., Kweon, G., Kwon, I. K., Yun, H., & Hong, J. T. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106423 · Cited by 36 · see citing works
Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow
Huang, T., Lu, Z., Wang, Z., Cheng, L., Gao, L., Gao, J., Zhang, N., Geng, C., Zhao, X., Wang, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48255-8 · Cited by 34 · see citing works
Beňová, A., Ferenčáková, M., Bardová, K., Funda, J., Procházka, J., Špoutil, F., Čajka, T., Dzubanova, M., Balcaen, T., Kerckhofs, G., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101598 · Cited by 34 · see citing works
“We hypothesized that MSDC-0602K might affect glutamine metabolism as MSDC-0602K treatment increased OB induction in primary mBM-MSCs, which is associated with increased glutamine metabolism [69].”
BackgroundSmall-molecule amines: a big role in the regulation of bone homeostasis
Zhang, Q., Yang, J., Hu, N., Liu, J., Yu, H., Pan, H., Chen, D., & Ruan, C. (2023) · Bone Research · doi:10.1038/s41413-023-00262-z · Cited by 34 · see citing works
“Gln generates important reducing substances such as glutathione and the nutrient glutamate in the body, all of which participate in nutrient metabolism, redox and energy metabolism via multiple signaling pathways, including the Wnt, mTOR, and reactive oxygen species (ROS) signaling pathways, to promote cell proliferat…”
BackgroundLi, Y., Wang, T., Li, X., Li, W., Lei, Y., Shang, Q., Zheng, Z., Fang, J., Cao, L., Yu, D., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.01.031 · Cited by 35 · see citing works
Chen, P., Hu, B., Xie, L., Jiang, T., Xia, Z., & Peng, H. (2021) · Cell Proliferation · doi:10.1111/cpr.13095 · Cited by 32 · see citing works
Yang, R., Zhang, X., Liu, J., Li, X., Zhou, D., & Luan, S. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.09.039 · Cited by 32 · see citing works
Current cutting-edge omics techniques on musculoskeletal tissues and diseases
Li, X., Fang, L., Zhou, R., Yao, L., Clayton, S. W., Muscat, S. N., Kamm, D. R., Wang, C., Liu, C.-J., Qin, L., et al. (2025) · Bone Research · doi:10.1038/s41413-025-00442-z · Cited by 31 · see citing works
“Stable isotope tracing has been particularly fruitful for tracing the fl ux of glucose and several different amino acids during osteoblast differentiation in cultured cells 193,194,197,198,221 and more recently in whole bones in vivo.”
Self-citationThe Amino Acid Sensor Eif2ak4/GCN2 Is Required for Proliferation of Osteoblast Progenitors in Mice
Hu, G., Yu, Y., Tang, Y. J., Wu, C., Long, F., & Karner, C. M. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4091 · Cited by 31 · see citing works
“known SSPC increase glutamine consumption and require glutamine metabolism to support proliferation,((15)) more broadly, the”
BackgroundSelf-citationPadthaisong, S., Phetcharaburanin, J., Klanrit, P., Li, J. V., Namwat, N., Khuntikeo, N., Titapun, A., Jarearnrat, A., Wangwiwatsin, A., Mahalapbutr, P., et al. (2021) · Cancer & Metabolism · doi:10.1186/s40170-021-00266-5 · Cited by 31 · see citing works
Nunn, E. R., Shinde, A. B., & Zaganjor, E. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.821278 · Cited by 32 · see citing works
Energy homeostasis in the bone
Zhou, M., An, Y.-Z., Guo, Q., Zhou, H., & Luo, X. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.12.009 · Cited by 32 · see citing works
Fu, D., Yang, S., Lu, J., Lian, H., & Qin, K. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02075-x · Cited by 30 · see citing works
“Recently, many studies have shown that BMSCs play an important role in the development of ONFH [29, 30].”
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Regulation of bone marrow mesenchymal stem cell fate by long non-coding RNA
Guo, Q., Guo, Q., Xiao, Y., Li, C., Huang, Y., & Luo, X. (2020) · Bone · doi:10.1016/j.bone.2020.115617 · Cited by 32 · see citing works
Role and mechanisms of autophagy in lung metabolism and repair
Li, X., Zhao, F., Wang, A., Cheng, P., & Chen, H. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03841-7 · Cited by 29 · see citing works
Schilling, K. J., Brown, E. B., & Zhang, X. (2021) · Bone · doi:10.1016/j.bone.2021.116257 · Cited by 29 · see citing works
Jiang, P., Hou, R., Chen, T., Bai, L., Li, J., Zhu, S., Wang, L., Willumeit‐Römer, R., & Guan, S. (2023) · Chemical Engineering Journal · doi:10.1016/j.cej.2023.143460 · Cited by 30 · see citing works
Epigenetic and "redoxogenetic" adaptation to physical exercise.
Radák, Z., Pan, L., Zhou, L., Mozaffaritabar, S., Gu, Y.-D., Pinho, R. A., Zheng, X., Ba, X.-Q., & Boldogh, I. (2023) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2023.11.005 · Cited by 26 · see citing works
Kamrani, S., Naseramini, R., Khani, P., Razavi, Z. S., Afkhami, H., Atashzar, M. R., Nasri, F., Alavimanesh, S., Saeidi, F., & Ronaghi, H. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03741-x · Cited by 27 · see citing works
“The degree of mineralization only increases when cells are provided with glucose and glutamine supplementation [64, 65].”
Lian, W., Wu, R., Lin, Y.-H., Chen, Y., Jahr, H., & Wang, F. (2024) · Antioxidants · doi:10.3390/antiox13040470 · Cited by 26 · see citing works
“…and dynamic bone formation capacity, as well as α -KG underproduction together with decreased osteogenic activity of bone marrow mesenchymal cells compared to wild-type mice. α -KG treatment preserves the growth and differentiation of mesenchymal stem cells in glutaminase knockout mice [56].”
Bispo, D. S. C., Jesus, C. S. H., Correia, M., Ferreira, F., Bonifazio, G., Goodfellow, B. J., Oliveira, M. B., Mano, J. F., & Gil, A. M. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00832 · Cited by 26 · see citing works
Sautchuk, R., Kalicharan, B. H., Escalera-Rivera, K., Jonason, J. H., Porter, G. A., Jr., Awad, H. A., & Eliseev, R. A. (2022) · eLife · doi:10.7554/elife.75023 · Cited by 26 · see citing works
Shen, Q., Zhang, C., Qin, X., Zhang, H., Zhang, Z., & Richel, A. (2021) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2021.118099 · Cited by 25 · see citing works
Self-citationMetabolic cross-talk within the bone marrow milieu: focus on multiple myeloma
Oudaert, I., der Vreken, A. V., Maes, A., Bruyne, E. D., Veirman, K. D., Vanderkerken, K., & Menu, E. (2022) · Experimental Hematology and Oncology · doi:10.1186/s40164-022-00303-z · Cited by 26 · see citing works
“Moreover, asparagine is also an important amino acid for the asparagine synthetase-dependent generation of osteoblasts, and is generated from glutamine [147, 148].”
BackgroundDa, W., Jiang, W., & Tao, L. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01835-5 · Cited by 24 · see citing works
“Finally, reducing the degradation of CS by MMP-9 to promote the production of net citric acid in the osteogenic differentiation of BMSCs may be a new direction of bone research.”
BackgroundAnwar, A., Sapra, L., Gupta, N., Ojha, R. P., Verma, B., & Srivastava, R. K. (2023) · Journal of Cellular Physiology · doi:10.1002/jcp.31036 · Cited by 24 · see citing works
“Proliferation and differentiation of mesenchymal stem cells into osteoblasts and chondrocytes and haematopoietic stem cells into osteoclasts is reported to be stimulated by active glutamine metabolism (Yu et al., 2019).”
BackgroundThe role of bone in whole-body energy metabolism
Lecka‐Czernik, B., Rosen, C. J., & Napoli, N. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01162-4 · Cited by 26 · see citing works
Huang, J.-W., Wu, L., Zhao, Y., & Zhao, H. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s514309 · Cited by 24 · see citing works
Glutamine-dependent signaling controls pluripotent stem cell fate
Lu, V., Roy, I. J., Torres, A., Joly, J. H., Ahsan, F. M., Graham, N. A., & Teitell, M. A. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.003 · Cited by 23 · see citing works
Integrative Analysis Reveals the Diverse Effects of 3D Stiffness upon Stem Cell Fate
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- Authors
- Yu, Y., Newman, H., Shen, L., Sharma, D., Hu, G., Mirando, A. J., Zhang, H., Knudsen, E., Zhang, G.-F., Hilton, M. J., & Karner, C. M.
- Affiliations
- Duke University (US)
- Corresponding author
- Karner, Courtney M.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 29
- Issue
- 4
- Pages
- 966-978.e4
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC7062112
- OpenAlex
- W2913128985
- Cited by
- 253
- References
- 69
- Citations by year
- 2026: 26 · 2025: 37 · 2024: 41 · 2023: 38 · 2022: 40 · 2021: 31 · 2020: 34 · 2019: 6
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (2AR063071, AR071967)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- skeletal stem cells, glutamine metabolism, glutaminase, osteogenic differentiation, adipogenesis, lineage specification, cell proliferation, alpha-ketoglutarate, transamination, bone formation, bone mass, osteoporosis, aging, stem cell expansion
- MeSH terms
- Animals, Cells, Cultured, Female, Glutamine, Male, Mice, Inbred Strains, Mass Spectrometry, Muscle, Skeletal, Cell Lineage, Myoblasts, Skeletal, Cell Proliferation, Mice
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