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Cited by 73Bone Metabolism and DiseasesMesenchymal stem cell researchAmino Acid Enzymes and Metabolism

Glutamine Metabolism Is Essential for Stemness of Bone Marrow Mesenchymal Stem Cells and Bone Homeostasis

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Zhou, Tao, Yang, Yuqing, Chen, Qianming, Xie, Liang·2019·Stem Cells International
DOI 10.1155/2019/8928934PMC PMC6757285
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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.

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  • Glutamine enhances the activity of glutaminase and glutamate dehydrogenase through the mTOR/S6 and MAPK signaling pathways, thereby stimulating cell proliferation.

    “According to reports, Gln enhances the activity of GLS (glutaminase) and GDH (Glutamate dehydrogenase) through the mTOR/S6 and MAPK signaling pathways, therefore stimulating cell proliferation [63].”

    From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [63]

  • Overexpression of immunological checkpoints, which reduces effector T cell activity, is one of the immune escape routes in MM.

    “The overexpression of immunological checkpoints, which reduces effector T cell activity, is one of the immune escape routes in MM [63].”

    From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [63]

    Section 3.3 discusses glutamine-dependent immunosuppressive effects of bone marrow mesenchymal stem cells, not immune-checkpoint overexpression in multiple myeloma. Searches for immune checkpoints, effector T cells, immune escape, MM, and PD-1/PD-L1 found no passage in our copy addressing the attributed claim. (LLM, conf=0.76)

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  1. [2]Katsimbri P. The biology of normal bone remodelling European Journal of Cancer Care 2017 26 6 10.1111/ecc.12740 2-s2.0-85032910870 28786518 · DOI
  2. [4]Fernandes T. A. P. Gonçalves L. M. L. Brito J. A. A. Relationships between bone turnover and energy metabolism Journal of Diabetes Research 2017 2017 11 10.1155/2017/9021314 2-s2.0-85021648613 28695134 PMC5485508 · DOI
  3. [5]Prideaux M. Findlay D. M. Atkins G. J. Osteocytes: the master cells in bone remodelling Current Opinion in Pharmacology 2016 28 24 30 10.1016/j.coph.2016.02.003 2-s2.0-84959354241 26927500 · DOI
  4. [6]Fukasawa K. Park G. Iezaki T. ATF3 controls proliferation of osteoclast precursor and bone remodeling Scientific Reports 2016 6 1 10.1038/srep30918 2-s2.0-84982717790 PMC4969588 27480204 · DOI
  5. [7]Suchacki K. J. Roberts F. Lovdel A. Skeletal energy homeostasis: a paradigm of endocrine discovery The Journal of Endocrinology 2017 234 1 R67 r79 10.1530/JOE-17-0147 2-s2.0-85023168053 28455432 · DOI
  6. [8]Rolfe D. F. Brown G. C. Cellular energy utilization and molecular origin of standard metabolic rate in mammals Physiological Reviews 1997 77 3 731 758 10.1152/physrev.1997.77.3.731 2-s2.0-0030854715 9234964 · DOI · Paper page
  7. [9]Hui S. Ghergurovich J. M. Morscher R. J. Glucose feeds the TCA cycle via circulating lactate Nature 2017 551 7678 115 118 10.1038/nature24057 2-s2.0-85032944832 29045397 PMC5898814 · DOI · Paper page
  8. [10]Porporato P. E. Payen V. L. Baselet B. Sonveaux P. Metabolic changes associated with tumor metastasis, part 2: mitochondria, lipid and amino acid metabolism Cellular and Molecular Life Sciences 2016 73 7 1349 1363 10.1007/s00018-015-2100-2 2-s2.0-84949506556 26646069 PMC11108268 · DOI
  9. [11]Kumar P. Dubey K. K. Modulation of fatty acid metabolism and tricarboxylic acid cycle to enhance the lipstatin production through medium engineering in Streptomyces toxytricini Bioresource Technology 2016 213 64 68 10.1016/j.biortech.2016.01.133 2-s2.0-84958231608 26897471 · DOI
  10. [12]Riddle R. C. Clemens T. L. Bone cell bioenergetics and skeletal energy homeostasis Physiological Reviews 2017 97 2 667 698 10.1152/physrev.00022.2016 2-s2.0-85013224896 28202599 PMC5539406 · DOI
  11. [13]Cooper M. S. Seibel M. J. Zhou H. Glucocorticoids, bone and energy metabolism Bone 2016 82 64 68 10.1016/j.bone.2015.05.038 2-s2.0-84954396126 26051468 · DOI
  12. [15]Huang H. Vandekeere S. Kalucka J. Role of glutamine and interlinked asparagine metabolism in vessel formation The EMBO Journal 2017 36 16 2334 2352 10.15252/embj.201695518 2-s2.0-85021440043 28659375 PMC5556263 · DOI · Paper page
  13. [16]Yao S. Li C. Beckley M. Liu D. Expression of odontogenic ameloblast-associated protein in the dental follicle and its role in osteogenic differentiation of dental follicle stem cells Archives of Oral Biology 2017 78 6 12 10.1016/j.archoralbio.2017.02.001 2-s2.0-85011976734 28189884 PMC5386806 · DOI
  14. [18]Olkku A. Mahonen A. Wnt and steroid pathways control glutamate signalling by regulating glutamine synthetase activity in osteoblastic cells Bone 2008 43 3 483 493 10.1016/j.bone.2008.04.016 2-s2.0-49149128088 18555765 · DOI
  15. [19]Stegen S. van Gastel N. Eelen G. HIF-1α Promotes Glutamine-Mediated Redox Homeostasis and Glycogen-Dependent Bioenergetics to Support Postimplantation Bone Cell Survival Cell Metabolism 2016 23 2 265 279 10.1016/j.cmet.2016.01.002 2-s2.0-84957941184 26863487 PMC7611069 · DOI
  16. [20]Shen G. Zhang H. Jia P. GOLM1 stimulation of glutamine metabolism promotes osteoporosis via inhibiting osteogenic differentiation of BMSCs Cellular Physiology and Biochemistry 2018 50 5 1916 1928 10.1159/000494872 2-s2.0-85056450902 30396165 · DOI
  17. [21]Mayers J. R. Vander Heiden M. G. Famine versus feast: understanding the metabolism of tumors in vivo Trends in Biochemical Sciences 2015 40 3 130 140 10.1016/j.tibs.2015.01.004 2-s2.0-84923186422 25639751 PMC4340757 · DOI
  18. [22]Bergstrom J. Furst P. Noree L. O. Vinnars E. Intracellular free amino acid concentration in human muscle tissue Journal of Applied Physiology 1974 36 6 693 697 10.1152/jappl.1974.36.6.693 4829908 · DOI · Paper page
  19. [23]Labow B. I. Souba W. W. Abcouwer S. F. Mechanisms governing the expression of the enzymes of glutamine metabolism--glutaminase and glutamine synthetase The Journal of Nutrition 2001 131 9 2467S 2474S 10.1093/jn/131.9.2467S 11533295 · DOI
  20. [24]Neu J. Shenoy V. Chakrabarti R. Glutamine nutrition and metabolism: where do we go from here? FASEB Journal 1996 10 8 829 837 10.1096/fasebj.10.8.8666159 8666159 · DOI
  21. [25]Moreadith R. W. Lehninger A. L. The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme The Journal of Biological Chemistry 1984 259 10 6215 6221 6144677
  22. [26]Hosios A. M. Hecht V. C. Danai L. V. Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells Developmental Cell 2016 36 5 540 549 10.1016/j.devcel.2016.02.012 2-s2.0-84959280789 26954548 PMC4766004 · DOI · Paper page
  23. [27]Alberghina L. Gaglio D. Redox control of glutamine utilization in cancer Cell Death & Disease 2014 5 12 p. e1561 10.1038/cddis.2014.513 2-s2.0-84926618247 PMC4454159 25476909 · DOI
  24. [29]Birsoy K. Wang T. Chen W. W. Freinkman E. Abu-Remaileh M. Sabatini D. M. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis Cell 2015 162 3 540 551 10.1016/j.cell.2015.07.016 2-s2.0-84938232611 26232224 PMC4522279 · DOI · Paper page
  25. [32]Still E. R. Yuneva M. O. Hopefully devoted to Q: targeting glutamine addiction in cancer British Journal of Cancer 2017 116 11 1375 1381 10.1038/bjc.2017.113 2-s2.0-85019841106 28441384 PMC5520092 · DOI
  26. [33]Le A. Lane A. N. Hamaker M. Glucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells Cell Metabolism 2012 15 1 110 121 10.1016/j.cmet.2011.12.009 2-s2.0-84855453655 22225880 PMC3345194 · DOI · Paper page
  27. [34]DeBerardinis R. J. Mancuso A. Daikhin E. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis Proceedings of the National Academy of Sciences of the United States of America 2007 104 49 19345 19350 10.1073/pnas.0709747104 2-s2.0-37449034854 18032601 PMC2148292 · DOI · Paper page
  28. [35]Cohen H. Barash H. Meivar-Levy I. The Wnt/β‐catenin pathway determines the predisposition and efficiency of liver‐to‐pancreas reprogramming Hepatology 2018 68 4 1589 1603 10.1002/hep.29827 2-s2.0-85054360835 29394503 · DOI
  29. [37]Palmieri E. M. Spera I. Menga A. Infantino V. Iacobazzi V. Castegna A. Glutamine synthetase desensitizes differentiated adipocytes to proinflammatory stimuli by raising intracellular glutamine levels FEBS Letters 2014 588 24 4807 4814 10.1016/j.febslet.2014.11.015 2-s2.0-84915755954 25451225 · DOI
  30. [38]Chisolm D. A. Weinmann A. S. Metabolites, genome organization, and cellular differentiation gene programs Current Opinion in Immunology 2018 51 62 67 10.1016/j.coi.2018.01.005 2-s2.0-85043315054 29525347 PMC6015741 · DOI
  31. [39]Biltz R. M. Letteri J. M. Pellegrino E. D. Palekar A. Pinkus L. M. Glutamine metabolism in bone Mineral and Electrolyte Metabolism 1983 9 3 125 131 6135980
  32. [40]Bianco P. Robey P. G. Skeletal stem cells Development 2015 142 6 1023 1027 10.1242/dev.102210 2-s2.0-84930532307 25758217 PMC4360182 · DOI · Paper page
  33. [41]Wu J. Zhang W. Ran Q. The differentiation balance of bone marrow mesenchymal stem cells is crucial to hematopoiesis Stem Cells International 2018 2018 13 10.1155/2018/1540148 2-s2.0-85056094931 29765406 PMC5903338 · DOI
  34. [42]Xie L. Zeng X. Hu J. Chen Q. Characterization of nestin, a selective marker for bone marrow derived mesenchymal stem cells Stem Cells International 2015 2015 9 10.1155/2015/762098 2-s2.0-84937707399 26236348 PMC4506912 · DOI
  35. [43]Nuschke A. Rodrigues M. Wells A. W. Sylakowski K. Wells A. Mesenchymal stem cells/multipotent stromal cells (MSCs) are glycolytic and thus glucose is a limiting factor of in vitro models of MSC starvation Stem Cell Research & Therapy 2016 7 1 p. 179 10.1186/s13287-016-0436-7 2-s2.0-85000366272 27906055 PMC5134064 · DOI
  36. [44]Tohyama S. Fujita J. Hishiki T. Glutamine oxidation is indispensable for survival of human pluripotent stem cells Cell Metabolism 2016 23 4 663 674 10.1016/j.cmet.2016.03.001 2-s2.0-84962069669 27050306 · DOI
  37. [45]Fillmore N. Huqi A. Jaswal J. S. Effect of fatty acids on human bone marrow mesenchymal stem cell energy metabolism and survival PLoS One 2015 10 3 10.1371/journal.pone.0120257 2-s2.0-84928922694 PMC4358990 25768019 · DOI
  38. [46]Borle A. B. Nichols N. Nichols G. Metabolic studies of bone in vitro. I. Normal bone The Journal of Biological Chemistry 1960 235 4 1206 1210 13802861
  39. [47]Dixon T. F. Perkins H. R. Citric acid and bone metabolism The Biochemical Journal 1952 52 2 260 265 10.1042/bj0520260 2-s2.0-0038219715 13018217 PMC1197978 · DOI
  40. [48]Costello L. C. Franklin R. B. Reynolds M. A. Chellaiah M. The important role of osteoblasts and citrate production in bone formation: “osteoblast citration” as a new concept for an old relationship, The Open Bone Journal 2012 4 1 27 34 10.2174/1876525401204010027 2-s2.0-84871027633 PMC3815682 24194797 · DOI
  41. [49]Covic A. Vervloet M. Massy Z. A. Bone and mineral disorders in chronic kidney disease: implications for cardiovascular health and ageing in the general population The Lancet Diabetes & Endocrinology 2018 6 4 319 331 10.1016/S2213-8587(17)30310-8 2-s2.0-85031506291 29050900 · DOI
  42. [50]Bonnet N. Bone-derived factors: a new gateway to regulate glycemia Calcified Tissue International 2017 100 2 174 183 10.1007/s00223-016-0210-y 2-s2.0-84994692103 27832316 · DOI
  43. [51]Thrailkill K. M. Nyman J. S. Bunn R. C. The impact of SGLT2 inhibitors, compared with insulin, on diabetic bone disease in a mouse model of type 1 diabetes Bone 2017 94 141 151 10.1016/j.bone.2016.10.026 2-s2.0-84994644951 27989651 PMC5826569 · DOI
  44. [52]Lee W. C. Guntur A. R. Long F. Rosen C. J. Energy metabolism of the osteoblast: implications for osteoporosis Endocrine Reviews 2017 38 3 255 266 10.1210/er.2017-00064 2-s2.0-85021763539 28472361 PMC5460680 · DOI · Paper page
  45. [54]Colombo S. L. Palacios-Callender M. Frakich N. Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells Proceedings of the National Academy of Sciences of the United States of America 2011 108 52 21069 21074 10.1073/pnas.1117500108 2-s2.0-84855476912 22106309 PMC3248543 · DOI
  46. [55]Ahn E. Kumar P. Mukha D. Tzur A. Shlomi T. Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle Molecular Systems Biology 2017 13 11 p. 953 10.15252/msb.20177763 2-s2.0-85035106623 PMC5731346 29109155 · DOI
  47. [56]Lenz P. Pfeiffer R. Baris D. Cell-cycle control in urothelial carcinoma: large-scale tissue array analysis of tumor tissue from Maine and Vermont Cancer Epidemiology, Biomarkers & Prevention 2012 21 9 1555 1564 10.1158/1055-9965.EPI-12-0261 2-s2.0-84866145906 22761304 PMC3480660 · DOI
  48. [57]Yuan L. Sheng X. Willson A. K. Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway Endocrine-Related Cancer 2015 22 4 577 591 10.1530/ERC-15-0192 2-s2.0-84940108436 26045471 PMC4500469 · DOI
  49. [58]Kim B. Li J. Jang C. Arany Z. Glutamine fuels proliferation but not migration of endothelial cells The EMBO Journal 2017 36 16 2321 2333 10.15252/embj.201796436 2-s2.0-85021438365 28659379 PMC5556269 · DOI
  50. [60]Gameiro P. A. Yang J. Metelo A. M. In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation Cell Metabolism 2013 17 3 372 385 10.1016/j.cmet.2013.02.002 2-s2.0-84875354450 23473032 PMC4003458 · DOI · Paper page
  51. [62]Chen C. T. Hsu S. H. Wei Y. H. Mitochondrial bioenergetic function and metabolic plasticity in stem cell differentiation and cellular reprogramming Biochimica et Biophysica Acta 2012 1820 5 571 576 10.1016/j.bbagen.2011.09.013 2-s2.0-84859424813 21983491 · DOI
  52. [63]Skerry T. M. The role of glutamate in the regulation of bone mass and architecture Journal of Musculoskeletal & Neuronal Interactions 2008 8 2 166 173 18622085
  53. [64]Deng L. Hong H. Zhang X. Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental follicle stem cells by epigenetically regulating Wnt pathway Biochemical and Biophysical Research Communications 2018 503 3 2061 2067 10.1016/j.bbrc.2018.07.160 2-s2.0-85051267054 30103943 · DOI
  54. [65]Chen Y. Yang Y. R. Fan X. L. miR-206 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells by targetting glutaminase Bioscience Reports 2019 39 3 p. BSR20181108 10.1042/bsr20181108 30804229 PMC6900431 · DOI
  55. [66]Wu H. Wu Z. Li P. Bone size and quality regulation: concerted actions of mTOR in mesenchymal stromal cells and osteoclasts Stem Cell Reports 2017 8 6 1600 1616 10.1016/j.stemcr.2017.04.005 2-s2.0-85018997158 28479301 PMC5469920 · DOI
  56. [68]Karner C. M. Esen E. Okunade A. L. Patterson B. W. Long F. Increased glutamine catabolism mediates bone anabolism in response to WNT signaling The Journal of Clinical Investigation 2015 125 2 551 562 10.1172/JCI78470 2-s2.0-84922147373 25562323 PMC4319407 · DOI
  57. [70]Carnesecchi J. Vanacker J. M. Estrogen-related receptors and the control of bone cell fate Molecular and Cellular Endocrinology 2016 432 37 43 10.1016/j.mce.2015.07.019 2-s2.0-84937703985 26206717 · DOI
  58. [71]Chen X. D. Shi S. Xu T. Robey P. G. Young M. F. Age-related osteoporosis in biglycan-deficient mice is related to defects in bone marrow stromal cells Journal of Bone and Mineral Research 2002 17 2 331 340 10.1359/jbmr.2002.17.2.331 2-s2.0-0036153106 11811564 · DOI
  59. [72]Wang T. He H. Liu S. Autophagy: a promising target for age-related osteoporosis Current Drug Targets 2019 20 3 354 365 10.2174/1389450119666180626120852 2-s2.0-85061144141 29943700 · DOI
  60. [73]Huang T. Liu R. Fu X. Aging reduces an ERRalpha-directed mitochondrial glutaminase expression suppressing glutamine anaplerosis and osteogenic differentiation of mesenchymal stem cells Stem Cells 2017 35 2 411 424 10.1002/stem.2470 2-s2.0-84983541131 27501743 · DOI
  61. [74]Bonnelye E. Reboul P. Duval N. Cardelli M. Aubin J. E. Estrogen receptor-related receptor α regulation by interleukin-1β in prostaglandin E2- and cAMP-dependent pathways in osteoarthritic chondrocytes Arthritis and Rheumatism 2011 63 8 2374 2384 10.1002/art.30398 2-s2.0-79961124749 21506092 · DOI
  62. [75]Bonnelye E. Laurin N. Jurdic P. Hart D. A. Aubin J. E. Estrogen receptor-related receptor-α (ERR-α) is dysregulated in inflammatory arthritis Rheumatology 2008 47 12 1785 1791 10.1093/rheumatology/ken368 2-s2.0-56649106684 18927192 · DOI
  63. [76]Gallet M. Saïdi S. Haÿ E. Repression of Osteoblast Maturation by ERRα Accounts for Bone Loss Induced by Estrogen Deficiency PLoS One 2013 8 1 p. e54837 10.1371/journal.pone.0054837 2-s2.0-84872865852 23359549 PMC3554601 · DOI
  64. [77]Luo C. Balsa E. Thomas A. ERRα Maintains Mitochondrial Oxidative Metabolism and Constitutes an Actionable Target in PGC1α-Elevated Melanomas Molecular Cancer Research 2017 15 10 1366 1375 10.1158/1541-7786.MCR-17-0143 2-s2.0-85030458173 28596418 PMC5954239 · DOI
  65. [78]Bonnelye E. Aubin J. E. An energetic orphan in an endocrine tissue: a revised perspective of the function of estrogen receptor-related receptor alpha in bone and cartilage Journal of Bone and Mineral Research 2013 28 2 225 233 10.1002/jbmr.1836 2-s2.0-84872440920 23212690 · DOI
  66. [79]Sabharwal S. S. Schumacker P. T. Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles’ heel? Nature Reviews. Cancer 2014 14 11 709 721 10.1038/nrc3803 2-s2.0-84908213474 25342630 PMC4657553 · DOI
  67. [80]Holzerova E. Prokisch H. Mitochondria: much ado about nothing? How dangerous is reactive oxygen species production? The International Journal of Biochemistry & Cell Biology 2015 63 16 20 10.1016/j.biocel.2015.01.021 2-s2.0-84939949923 25666559 PMC4444525 · DOI
  68. [81]Geng W. Shi H. Zhang X. Tan W. Cao Y. Mei R. Substance P enhances BMSC osteogenic differentiation via autophagic activation Molecular Medicine Reports 2019 20 1 664 670 10.3892/mmr.2019.10257 31115537 PMC6580032 · DOI
  69. [82]Shyh-Chang N. Daley G. Q. Cantley L. C. Stem cell metabolism in tissue development and aging Development 2013 140 12 2535 2547 10.1242/dev.091777 2-s2.0-84875953755 23715547 PMC3666381 · DOI
  70. [84]Singh K. Krug L. Basu A. Alpha-ketoglutarate curbs differentiation and induces cell death in mesenchymal stromal precursors with mitochondrial dysfunction Stem Cells 2017 35 7 1704 1718 10.1002/stem.2629 2-s2.0-85018968890 28398002 · DOI
  71. [85]Tormos K. V. Anso E. Hamanaka R. B. Mitochondrial complex III ROS regulate adipocyte differentiation Cell Metabolism 2011 14 4 537 544 10.1016/j.cmet.2011.08.007 2-s2.0-80053904684 21982713 PMC3190168 · DOI
  72. [86]Wang W. Zhang Y. Lu W. Liu K. Mitochondrial reactive oxygen species regulate adipocyte differentiation of mesenchymal stem cells in hematopoietic stress induced by arabinosylcytosine PLoS One 2015 10 3 p. e0120629 10.1371/journal.pone.0120629 2-s2.0-84928796551 PMC4359087 25768922 · DOI
  73. [87]Bernardo M. E. Fibbe W. E. Mesenchymal stromal cells and hematopoietic stem cell transplantation Immunology Letters 2015 168 2 215 221 10.1016/j.imlet.2015.06.013 2-s2.0-84949626345 26116911 · DOI
  74. [88]Lee M. W. Ryu S. Kim D. S. Sung K. W. Koo H. H. Yoo K. H. Strategies to improve the immunosuppressive properties of human mesenchymal stem cells Stem Cell Research & Therapy 2015 6 1 10.1186/s13287-015-0178-y 2-s2.0-84943250221 PMC4596374 26445096 · DOI
  75. [89]Wang M. Yuan Q. Xie L. Mesenchymal stem cell-based immunomodulation: properties and clinical application Stem Cells International 2018 2018 12 10.1155/2018/3057624 2-s2.0-85051462590 30013600 PMC6022321 · DOI
  76. [90]Sasaki E. Umeda T. Takahashi I. Effect of glutamine supplementation on neutrophil function in male judoists Luminescence 2013 28 4 442 449 10.1002/bio.2474 2-s2.0-84881376791 23348981 · DOI
  77. [91]Sartori T. Galvão dos Santos G. Nogueira-Pedro A. Effects of glutamine, taurine and their association on inflammatory pathway markers in macrophages Inflammopharmacology 2018 26 3 829 838 10.1007/s10787-017-0406-4 2-s2.0-85031911183 29052795 · DOI
  78. [92]Wasinski F. Gregnani M. F. Ornellas F. H. Lymphocyte glucose and glutamine metabolism as targets of the anti-inflammatory and immunomodulatory effects of exercise Mediators of Inflammation 2014 2014 10 10.1155/2014/326803 2-s2.0-84903639463 24987195 PMC4060061 · DOI
  79. [93]Qian D. Wei G. Xu C. Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats Scientific Reports 2017 7 1 p. 581 10.1038/s41598-017-00629-3 2-s2.0-85017093672 28373667 PMC5428835 · DOI
  80. [94]Ganesan R. Rasool M. Interleukin 17 regulates SHP-2 and IL-17RA/STAT-3 dependent Cyr61, IL-23 and GM-CSF expression and RANKL mediated osteoclastogenesis by fibroblast-like synoviocytes in rheumatoid arthritis Molecular Immunology 2017 91 134 144 10.1016/j.molimm.2017.09.003 2-s2.0-85028988849 28898718 · DOI
  81. [95]Sun Y. Ma J. Li D. Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures Journal of Neuroinflammation 2019 16 1 p. 66 10.1186/s12974-019-1452-1 30922332 PMC6437919 · DOI
  82. [96]Levy D. E. Lee C. K. What does Stat3 do? The Journal of Clinical Investigation 2002 109 9 1143 1148 10.1172/JCI0215650 2-s2.0-0036256644 11994402 PMC150972 · DOI · Paper page
  83. [97]Dos Santos G. G. Hastreiter A. A. Sartori T. Borelli P. Fock R. A. L-Glutamine in vitro modulates some immunomodulatory properties of bone marrow mesenchymal stem cells Stem Cell Reviews and Reports 2017 13 4 482 490 10.1007/s12015-017-9746-0 2-s2.0-85020276492 28593472 · DOI
  84. [98]Sukho P. Hesselink J. W. Kops N. Kirpensteijn J. Verseijden F. Bastiaansen-Jenniskens Y. M. Human mesenchymal stromal cell sheets induce macrophages predominantly to an anti-inflammatory phenotype Stem Cells and Development 2018 27 13 922 934 10.1089/scd.2017.0275 2-s2.0-85049759299 29737241 · DOI
  85. [99]Capulli M. Paone R. Rucci N. Osteoblast and osteocyte: games without frontiers Archives of Biochemistry and Biophysics 2014 561 3 12 10.1016/j.abb.2014.05.003 2-s2.0-84907939190 24832390 · DOI · Paper page
  86. [101]Bellon G. Chaqour B. Wegrowski Y. Monboisse J. C. Borel J. P. Glutamine increases collagen gene transcription in cultured human fibroblasts Biochimica et Biophysica Acta 1995 1268 3 311 323 10.1016/0167-4889(95)00093-8 2-s2.0-0029125217 7548230 · DOI
  87. [102]Masson J. Darmon M. Conjard A. Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth The Journal of Neuroscience 2006 26 17 4660 4671 10.1523/JNEUROSCI.4241-05.2006 2-s2.0-33646852395 16641247 PMC2745954 · DOI
  88. [103]Melrose J. Shu C. Whitelock J. M. Lord M. S. The cartilage extracellular matrix as a transient developmental scaffold for growth plate maturation Matrix Biology 2016 52-54 363 383 10.1016/j.matbio.2016.01.008 2-s2.0-84956690364 26807757 · DOI · Paper page
  89. [104]Handley C. J. Speight G. Leyden K. M. Lowther D. A. Extracellular matrix metabolism by chondrocytes 7. Evidence that L-glutamine is an essential amino acid for chondrocytes and other connective tissue cells Biochimica et Biophysica Acta 1980 627 3 324 331 10.1016/0304-4165(80)90463-8 2-s2.0-0018829127 6101542 · DOI
  90. [105]Rajpurohit R. Koch C. J. Tao Z. Teixeira C. M. Shapiro I. M. Adaptation of chondrocytes to low oxygen tension: relationship between hypoxia and cellular metabolism Journal of Cellular Physiology 1996 168 2 424 432 10.1002/(SICI)1097-4652(199608)168:2<424::AID-JCP21>3.0.CO;2-1 8707878 · DOI
  91. [106]Maes C. Araldi E. Haigh K. VEGF-independent cell-autonomous functions of HIF-1α regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival Journal of Bone and Mineral Research 2012 27 3 596 609 10.1002/jbmr.1487 2-s2.0-84857316278 22162090 · DOI
  92. [107]Yu J. Liang F. Huang H. Pirttiniemi P. Yu D. Effects of loading on chondrocyte hypoxia, HIF-1α and VEGF in the mandibular condylar cartilage of young rats Orthodontics & Craniofacial Research 2018 21 1 41 47 10.1111/ocr.12212 2-s2.0-85038873117 29271061 · DOI
  93. [108]Stegen S. Laperre K. Eelen G. HIF-1α metabolically controls collagen synthesis and modification in chondrocytes Nature 2019 565 7740 511 515 10.1038/s41586-019-0874-3 2-s2.0-85060379292 30651640 PMC7195049 · DOI
  94. [109]Gouze J. N. Bordji K. Gulberti S. Interleukin‐1β down‐regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: Influence of glucosamine on interleukin‐1β–mediated effects in rat chondrocytes Arthritis and Rheumatism 2001 44 2 351 360 10.1002/1529-0131(200102)44:2<351::AID-ANR53>3.0.CO;2-M 11229466 · DOI
  95. [110]Issa R. Boeving M. Kinter M. Griffin T. M. Effect of biomechanical stress on endogenous antioxidant networks in bovine articular cartilage Journal of Orthopaedic Research 2018 36 2 760 769 10.1002/jor.23728 2-s2.0-85042942121 28892196 PMC5839935 · DOI
  96. [111]Tonomura H. Takahashi K. A. Mazda O. Glutamine protects articular chondrocytes from heat stress and NO-induced apoptosis with HSP70 expression Osteoarthritis and Cartilage 2006 14 6 545 553 10.1016/j.joca.2005.12.008 2-s2.0-33646771362 16480901 · DOI
  97. [112]Kim J. H. Kim K. Kim I. Seong S. Lee K. B. Kim N. BCAP promotes osteoclast differentiation through regulation of the p38-dependent CREB signaling pathway Bone 2018 107 188 195 10.1016/j.bone.2017.12.005 2-s2.0-85037659189 29223746 · DOI
  98. [113]Indo Y. Takeshita S. Ishii K. A. Metabolic regulation of osteoclast differentiation and function Journal of Bone and Mineral Research 2013 28 11 2392 2399 10.1002/jbmr.1976 2-s2.0-84886859944 23661628 · DOI
  99. [114]Utsunomiya-Tate N. Endou H. Kanai Y. Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter The Journal of Biological Chemistry 1996 271 25 14883 14890 10.1074/jbc.271.25.14883 2-s2.0-0029888341 8662767 · DOI
  100. [115]Nicklin P. Bergman P. Zhang B. Bidirectional transport of amino acids regulates mTOR and autophagy Cell 2009 136 3 521 534 10.1016/j.cell.2008.11.044 2-s2.0-59049087460 19203585 PMC3733119 · DOI · Paper page
  101. [116]Cooney G. Curi R. Mitchelson A. Newsholme P. Simpson M. Newsholme E. A. Activities of some key enzymes of carbohydrate, ketone body, adenosine and glutamine metabolism in liver, and brown and white adipose tissues of the rat Biochemical and Biophysical Research Communications 1986 138 2 687 692 10.1016/S0006-291X(86)80551-4 2-s2.0-0022492608 3741427 · DOI
  102. [117]DeBerardinis R. J. Lum J. J. Hatzivassiliou G. Thompson C. B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation Cell Metabolism 2008 7 1 11 20 10.1016/j.cmet.2007.10.002 2-s2.0-37449024702 18177721 · DOI · Paper page
  103. [118]Soh H. Wasa M. Fukuzawa M. Hypoxia upregulates amino acid transport in a human neuroblastoma cell line Journal of Pediatric Surgery 2007 42 4 608 612 10.1016/j.jpedsurg.2006.12.010 2-s2.0-34247121454 17448754 · DOI
  104. [119]Morten K. J. Badder L. Knowles H. J. Differential regulation of HIF-mediated pathways increases mitochondrial metabolism and ATP production in hypoxic osteoclasts The Journal of Pathology 2013 229 5 755 764 10.1002/path.4159 2-s2.0-84875043252 23303559 PMC3618370 · DOI
  105. [122]Benjamin J. Makharia G. Ahuja V. Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn’s disease: a randomized controlled trial Digestive Diseases and Sciences 2012 57 4 1000 1012 10.1007/s10620-011-1947-9 2-s2.0-84864064947 22038507 · DOI
  106. [123]Byrne T. A. Wilmore D. W. Iyer K. Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial Annals of Surgery 2005 242 5 655 661 10.1097/01.sla.0000186479.53295.14 2-s2.0-23844465080 16244538 PMC1409868 · DOI
  107. [124]Wu G. H. Wu Z. H. Wu Z. G. Effects of bowel rehabilitation and combined trophic therapy on intestinal adaptation in short bowel patients World Journal of Gastroenterology 2003 9 11 2601 2604 10.3748/wjg.v9.i11.2601 2-s2.0-0344467345 14606106 PMC4656550 · DOI
  108. [125]Guo M. Li Y. Li J. Effect of growth hormone, glutamine, and enteral nutrition on intestinal adaptation in patients with short bowel syndrome The Turkish Journal of Gastroenterology 2013 24 6 463 468 10.4318/tjg.2013.0555 2-s2.0-84894177161 24623283 · DOI
  109. [126]Liu X. Sun X. F. Ge Q. X. The role of glutamine supplemented total parenteral nutrition (TPN) in severe acute pancreatitis European Review for Medical and Pharmacological Science 2016 20 19 4176 4180 27775778
  110. [127]de Beaux A. C. O’Riordain M. G. Ross J. A. Jodozi L. Carter D. C. Fearon K. C. H. Glutamine-supplemented total parenteral nutrition reduces blood mononuclear cell interleukin-8 release in severe acute pancreatitis Nutrition 1998 14 3 261 265 10.1016/S0899-9007(97)00477-2 2-s2.0-0032031166 9583368 · DOI
  111. [128]Masini A. Efrati C. Merli M. Effect of blood ammonia elevation following oral glutamine load on the psychometric performance of cirrhotic patients Metabolic Brain Disease 2003 18 1 27 35 10.1023/A:1021926601907 2-s2.0-0037369016 12603080 · DOI
  112. [129]Niihara Y. Miller S. T. Kanter J. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease The New England Journal of Medicine 2018 379 3 226 235 10.1056/NEJMoa1715971 2-s2.0-85050508815 30021096 · DOI
  113. [130]Wilmore D. W. Food and Drug Administration approval of glutamine for sickle cell disease: success and precautions in glutamine research Journal of Parenteral and Enteral Nutrition 2017 41 6 912 917 10.1177/0148607117727271 2-s2.0-85030693051 28858569 · DOI
  114. [131]Wu C. Kato T. S. Ji R. Supplementation ofl-Alanyl-l-Glutamine and Fish Oil Improves Body Composition and Quality of Life in Patients With Chronic Heart Failure Circulation. Heart Failure 2015 8 6 1077 1087 10.1161/CIRCHEARTFAILURE.115.002073 2-s2.0-84947804753 26269566 PMC4802502 · DOI
  115. [132]Mok E. Violante C. E. D. Daubrosse C. Oral glutamine and amino acid supplementation inhibit whole-body protein degradation in children with Duchenne muscular dystrophy The American Journal of Clinical Nutrition 2006 83 4 823 828 10.1093/ajcn/83.4.823 16600934 · DOI
  116. [133]Letellier G. Mok E. Alberti C. Effect of glutamine on glucose metabolism in children with Duchenne muscular dystrophy Clinical Nutrition 2013 32 3 386 390 10.1016/j.clnu.2012.08.019 2-s2.0-84877115037 23021433 · DOI
  117. [134]Jordan I. Balaguer M. Esteban M. E. Glutamine effects on heat shock protein 70 and interleukines 6 and 10: randomized trial of glutamine supplementation versus standard parenteral nutrition in critically ill children Clinical Nutrition 2016 35 1 34 40 10.1016/j.clnu.2015.01.019 2-s2.0-84923071901 25701159 · DOI
  118. [135]Koksal G. M. Erbabacan E. Tunali Y. Karaoren G. Vehid S. Oz H. The effects of intravenous, enteral and combined administration of glutamine on malnutrition in sepsis: a randomized clinical trial Asia Pacific Journal of Clinical Nutrition 2014 23 1 34 40 24561970
  119. [136]Lacey J. M. Crouch J. B. Benfell K. The effects of glutamine-supplemented parenteral nutrition in premature infants Journal of Parenteral and Enteral Nutrition 1996 20 1 74 80 10.1177/014860719602000174 2-s2.0-0030071930 8788268 · DOI
  120. [137]Ehrenkranz R. A. Das A. Wrage L. A. Early nutrition mediates the influence of severity of illness on extremely LBW infants Pediatric Research 2011 69 6 522 529 10.1203/PDR.0b013e318217f4f1 2-s2.0-79955840963 21378596 PMC3090495 · DOI
  121. [138]Dunphy M. P. S. Harding J. J. Venneti S. In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of18F-(2S,4R)-4-Fluoroglutamine Radiology 2018 287 2 667 675 10.1148/radiol.2017162610 2-s2.0-85046024861 29388903 PMC5929369 · DOI
  122. [139]Eda K. Uzer K. Murat T. Cenk U. The effects of enteral glutamine on radiotherapy induced dermatitis in breast cancer Clinical Nutrition 2016 35 2 436 439 10.1016/j.clnu.2015.03.009 2-s2.0-84960484455 25869479 · DOI
  123. [140]Kucuktulu E. Guner A. Kahraman I. Topbas M. Kucuktulu U. The protective effects of glutamine on radiation-induced diarrhea Supportive Care in Cancer 2013 21 4 1071 1075 10.1007/s00520-012-1627-0 2-s2.0-84879795964 23064902 · DOI
  124. [141]TSUJIMOTO T. A. K. A. E. YAMAMOTO Y. WASA M. L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer: A double-blind, randomized, placebo-controlled trial Oncology Reports 2015 33 1 33 39 10.3892/or.2014.3564 2-s2.0-84916197574 25351453 PMC4254677 · DOI
  125. [142]Tanaka Y. Takahashi T. Yamaguchi K. Osada S. Shimokawa T. Yoshida K. Elemental diet plus glutamine for the prevention of mucositis in esophageal cancer patients receiving chemotherapy: a feasibility study Supportive Care in Cancer 2016 24 2 933 941 10.1007/s00520-015-2864-9 2-s2.0-84952872732 26266659 PMC4689762 · DOI
  126. [143]Chang S. C. Lai Y. C. Hung J. C. Chang C. Y. Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer Medicine (Baltimore) 2019 98 8 p. e14463 10.1097/MD.0000000000014463 2-s2.0-85062759646 30813149 PMC6408144 · DOI
  127. [144]Sands S. Ladas E. J. Kelly K. M. Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer Supportive Care in Cancer 2017 25 3 701 708 10.1007/s00520-016-3441-6 2-s2.0-84994448288 27830395 PMC5598352 · DOI
  128. [145]Piccirillo N. de Matteis S. Laurenti L. Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis Haematologica 2003 88 2 192 200 12604409
  129. [146]Pytlik R. Gregora E. Benes P. Kozak T. Effect of parenteral glutamine on restoration of lymphocyte subpopulations after high-dose chemotherapy and autologous hematopoietic cell transplantation: data from a double-blind randomized study Epidemiologie, Mikrobiologie, Imunologie 2002 51 4 152 155 12532901
  130. [147]Barros M. A. P. Vasconcelos P. R. L. Souza C. M. L-Alanyl-glutamine attenuates oxidative stress in liver transplantation patients Transplantation Proceedings 2015 47 8 2478 2482 10.1016/j.transproceed.2015.08.001 2-s2.0-84945945475 26518955 · DOI
  131. [148]Hissa M. N. Vasconcelos R. C.. Guimarães S. B. Silva R. P. Garcia J. H. P. Vasconcelos P. R. L.. Preoperative glutamine infusion improves glycemia in heart surgery patients Acta Cirurgica Brasileira 2011 26 Suppl 1 77 81 10.1590/S0102-86502011000700016 21971663 · DOI
  132. [149]Chávez-Tostado M. Carrillo-Llamas F. Martínez-Gutiérrez P. E. Oral glutamine reduces myocardial damage after coronary revascularization under cardiopulmonary bypass. A randomized clinical trial Nutrición Hospitalaria 2017 34 2 277 283 10.20960/nh.519 2-s2.0-85018804173 28421779 · DOI
  133. [150]Nishizaki K. Ikegami H. Tanaka Y. Imai R. Matsumura H. Effects of supplementation with a combination of β-hydroxy-β-methyl butyrate, L-arginine, and L-glutamine on postoperative recovery of quadriceps muscle strength after total knee arthroplasty Asia Pacific Journal of Clinical Nutrition 2015 24 3 412 420 26420181
  134. [151]Eisman J. A. Bogoch E. R. Dell R. Making the first fracture the last fracture: ASBMR task force report on secondary fracture prevention Journal of Bone and Mineral Research 2012 27 10 2039 2046 10.1002/jbmr.1698 2-s2.0-84866662641 22836222 · DOI
  135. [152]Polat O. Kilicoglu S. S. Erdemli E. A controlled trial of glutamine effects on bone healing Advances in Therapy 2007 24 1 154 160 10.1007/BF02850003 2-s2.0-34247853342 17526472 · DOI
  136. [153]TOMASZEWSKA E. DOBROWOLSKI P. PROST Ł. HUŁAS-STASIAK M. MUSZYŃSKI S. BLICHARSKI T. The effect of supplementation of a glutamine precursor on the growth plate, articular cartilage and cancellous bone in fundectomy-induced osteopenic bone The Journal of Veterinary Medical Science 2016 78 4 563 571 10.1292/jvms.15-0385 2-s2.0-84964902314 26725871 PMC4873845 · DOI
  137. [154]Dobrowolski P. Tomaszewska E. Muszynski S. Blicharski T. Pierzynowski S. G. Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose Experimental Biology and Medicine 2017 242 7 671 682 10.1177/1535370217693322 2-s2.0-85015732603 28178857 PMC5363691 · DOI
  138. [155]Thomas A. C. Hubbard-Turner T. Wikstrom E. A. Palmieri-Smith R. M. Epidemiology of posttraumatic osteoarthritis Journal of Athletic Training 2017 52 6 491 496 10.4085/1062-6050-51.5.08 2-s2.0-85021386067 27145096 PMC5488839 · DOI
  139. [156]Fujita S. Arai Y. Nakagawa S. Combined microwave irradiation and intraarticular glutamine administration-induced HSP70 expression therapy prevents cartilage degradation in a rat osteoarthritis model Journal of Orthopaedic Research 2012 30 3 401 407 10.1002/jor.21535 2-s2.0-84873036533 21853458 · DOI
  140. [157]Mehrabani D. Babazadeh M. Tanideh N. The healing effect of adipose-derived mesenchymal stem cells in full-thickness femoral articular cartilage defects of rabbit International Journal of Organ Transplantation Medicine 2015 6 4 165 175 26576262 PMC4644569

Cited by

Sorted by citations

Authors
Zhou, T., Yang, Y., Chen, Q., & Xie, L.
Affiliations
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Xie, Liang
ORCID
Venue
Stem Cells International
Publisher
Wiley
Published
2019-09-12
Volume
2019
Pages
1-13
ISSN
  • 1687-966X (ISSN-L)
  • 1687-9678
DOI
10.1155/2019/8928934
PMC
PMC6757285
OpenAlex
W2972453102
Cited by
73
References
18
Citations by year
2026: 6 · 2025: 11 · 2024: 14 · 2023: 8 · 2022: 15 · 2021: 15 · 2020: 4
FWCI
0.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cells International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Sichuan University (2018SCUH0056, 81600842, 81621062, 81520108009)
  • National Natural Science Foundation of China (2018SCUH0056, 81600842, 81621062, 81520108009)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
glutamine metabolism, bone marrow mesenchymal stem cells, stemness, bone homeostasis, Wnt signaling, mTOR signaling, reactive oxygen species, osteoblast mineralization, osteoclasts, bone resorption, osteoporosis, osteoarthritis, degenerative bone disease, glutamine supplementation

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