
Role of amino acid metabolism in osteoporosis: Effects on the bone microenvironment and treatment strategies (Review)
- Authors:
- Chang Zhou
- Jiaheng Zhang
- Qizhi Liu
- Yanghongxu Guo
- Mengyuan Li
- Jing Tao
- Sujuan Peng
- Ronghui Li
- Xianguang Deng
- Guomin Zhang
- Huiping Liu
-
Affiliations: College of Integrative Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208, P.R. China - Published online on: May 26, 2025 https://doi.org/10.3892/mmr.2025.13577
- Article Number: 212
-
Copyright : © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
This article is mentioned in:
Abstract
![]() |
![]() |
Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O'Karma M, Wallace TC and Zemel BS: The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: A systematic review and implementation recommendations. Osteoporos Int. 27:1281–1386. 2016. View Article : Google Scholar : PubMed/NCBI | |
Rozenberg S, Bruyère O, Bergmann P, Cavalier E, Gielen E, Goemaere S, Kaufman JM, Lapauw B, Laurent MR, De Schepper J and Body JJ: How to manage osteoporosis before the age of 50. Maturitas. 138:14–25. 2020. View Article : Google Scholar : PubMed/NCBI | |
Wu Y, Xie L, Wang M, Xiong Q, Guo Y, Liang Y, Li J, Sheng R, Deng P, Wang Y, et al: Mettl3-mediated mA RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis. Nat Commun. 9:47722018. View Article : Google Scholar : PubMed/NCBI | |
Lademann F, Tsourdi E, Hofbauer LC and Rauner M: Thyroid hormone actions and bone remodeling-the role of the wnt signaling pathway. Exp Clin Endocrinol Diabetes. 128:450–454. 2020. View Article : Google Scholar : PubMed/NCBI | |
Shen Y, Huang X, Wu J, Lin X, Zhou X, Zhu Z, Pan X, Xu J, Qiao J, Zhang T, et al: The Global Burden of osteoporosis, low bone mass, and its related fracture in 204 countries and territories, 1990–2019. Front Endocrinol (Lausanne). 13:8822412022. View Article : Google Scholar : PubMed/NCBI | |
Johnston CB and Dagar M: Osteoporosis in older adults. Med Clin North Am. 104:873–884. 2020. View Article : Google Scholar : PubMed/NCBI | |
Confavreux CB, Levine RL and Karsenty G: A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms. Mol Cell Endocrinol. 310:21–29. 2009. View Article : Google Scholar : PubMed/NCBI | |
Cao S, Li Y, Song R, Meng X, Fuchs M, Liang C, Kachler K, Meng X, Wen J, Schlötzer-Schrehardt U, et al: L-arginine metabolism inhibits arthritis and inflammatory bone loss. Ann Rheum Dis. 83:72–87. 2024. View Article : Google Scholar : PubMed/NCBI | |
Panahi N, Fahimfar N, Roshani S, Arjmand B, Gharibzadeh S, Shafiee G, Migliavacca E, Breuille D, Feige JN, Grzywinski Y, et al: Association of amino acid metabolites with osteoporosis, a metabolomic approach: Bushehr elderly health program. Metabolomics. 18:632022. View Article : Google Scholar : PubMed/NCBI | |
Wilson MP, Plecko B, Mills PB and Clayton PT: Disorders affecting vitamin B6 metabolism. J Inherit Metab Dis. 42:629–646. 2019. View Article : Google Scholar : PubMed/NCBI | |
Montalvany-Antonucci CC, Duffles LF, de Arruda JAA, Zicker MC, de Oliveira S, Macari S, Garlet GP, Madeira MFM, Fukada SY, Andrade I Jr, et al: Short-chain fatty acids and FFAR2 as suppressors of bone resorption. Bone. 125:112–121. 2019. View Article : Google Scholar : PubMed/NCBI | |
Lucas S, Omata Y, Hofmann J, Böttcher M, Iljazovic A, Sarter K, Albrecht O, Schulz O, Krishnacoumar B, Krönke G, et al: Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun. 9:552018. View Article : Google Scholar : PubMed/NCBI | |
Prockop DJ and Kivirikko KI: Collagens: Molecular biology, diseases, and potentials for therapy. Annu Rev Biochem. 64:403–434. 1995. View Article : Google Scholar : PubMed/NCBI | |
Shoulders MD and Raines RT: Collagen structure and stability. Annu Rev Biochem. 78:929–958. 2009. View Article : Google Scholar : PubMed/NCBI | |
Whyte MP: Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci. 1192:190–200. 2010. View Article : Google Scholar : PubMed/NCBI | |
Heaney RP and Layman DK: Amount and type of protein influences bone health. Am J Clin Nutr. 87:1567S–1570S. 2008. View Article : Google Scholar : PubMed/NCBI | |
Ding KH, Cain M, Davis M, Bergson C, McGee-Lawrence M, Perkins C, Hardigan T, Shi X, Zhong Q, Xu J, et al: Amino acids as signaling molecules modulating bone turnover. Bone. 115:15–24. 2018. View Article : Google Scholar : PubMed/NCBI | |
Long F: Energy metabolism and bone. Bone. 115:12018. View Article : Google Scholar : PubMed/NCBI | |
Dirckx N, Moorer MC, Clemens TL and Riddle RC: The role of osteoblasts in energy homeostasis. Nat Rev Endocrinol. 15:651–665. 2019. View Article : Google Scholar : PubMed/NCBI | |
Lv Z, Shi W and Zhang Q: Role of essential amino acids in age-induced bone loss. Int J Mol Sci. 23:112812022. View Article : Google Scholar : PubMed/NCBI | |
Devignes CS, Carmeliet G and Stegen S: Amino acid metabolism in skeletal cells. Bone Rep. 17:1016202022. View Article : Google Scholar : PubMed/NCBI | |
Xu F, Li W, Yang X, Na L, Chen L and Liu G: The roles of epigenetics regulation in bone metabolism and osteoporosis. Front Cell Dev Biol. 8:6193012021. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Huang X, Zhang X and Chen Z: Metabolism-epigenetic interaction-based bone and dental regeneration: From impacts and mechanisms to treatment potential. Bone. 192:1173822025. View Article : Google Scholar : PubMed/NCBI | |
Yang L, Chu Z, Liu M, Zou Q, Li J, Liu Q, Wang Y, Wang T, Xiang J and Wang B: Amino acid metabolism in immune cells: Essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy. J Hematol Oncol. 16:592023. View Article : Google Scholar : PubMed/NCBI | |
Karner CM and Long F: Glucose metabolism in bone. Bone. 115:2–7. 2018. View Article : Google Scholar : PubMed/NCBI | |
Alekos NS, Moorer MC and Riddle RC: Dual effects of lipid metabolism on osteoblast function. Front Endocrinol (Lausanne). 11:5781942020. View Article : Google Scholar : PubMed/NCBI | |
Cui Z, Feng H, He B, He J and Tian Y: Relationship between serum amino acid levels and bone mineral density: A mendelian randomization study. Front Endocrinol (Lausanne). 12:7635382021. View Article : Google Scholar : PubMed/NCBI | |
Liao M, Mu Y, Su X, Zheng L, Zhang S, Chen H, Xu S, Ma J, Ouyang R, Li W, et al: Association between Branched-Chain Amino Acid Intake and Physical Function among Chinese Community-Dwelling Elderly Residents. Nutrients. 14:43672022. View Article : Google Scholar : PubMed/NCBI | |
Kim M, Isoda H and Okura T: Effect of Citrulline and leucine intake with exercises on body composition, physical activity, and amino acid concentration in older women: A Randomized double-blind placebo-controlled study. Foods. 10:31172021. View Article : Google Scholar : PubMed/NCBI | |
Kirk B, Mooney K, Vogrin S, Jackson M, Duque G, Khaiyat O and Amirabdollahian F: Leucine-enriched whey protein supplementation, resistance-based exercise, and cardiometabolic health in older adults: A randomized controlled trial. J Cachexia Sarcopenia Muscle. 12:2022–2033. 2021. View Article : Google Scholar : PubMed/NCBI | |
Refaey ME, Zhong Q, Ding KH, Shi XM, Xu J, Bollag WB, Hill WD, Chutkan N, Robbins R, Nadeau H, et al: Impact of dietary aromatic amino acids on osteoclastic activity. Calcif Tissue Int. 95:174–182. 2014. View Article : Google Scholar : PubMed/NCBI | |
Michalowska M, Znorko B, Kaminski T, Oksztulska-Kolanek E and Pawlak D: New insights into tryptophan and its metabolites in the regulation of bone metabolism. J Physiol Pharmacol. 66:779–791. 2015.PubMed/NCBI | |
Akinsuyi OS and Roesch LFW: Meta-analysis reveals compositional and functional microbial changes associated with osteoporosis. Microbiol Spectr. 11:e00322232023. View Article : Google Scholar : PubMed/NCBI | |
Kim BJ, Hamrick MW, Yoo HJ, Lee SH, Kim SJ, Koh JM and Isales CM: The detrimental effects of kynurenine, a tryptophan metabolite, on human bone metabolism. J Clin Endocrinol Metab. 104:2334–2342. 2019. View Article : Google Scholar : PubMed/NCBI | |
Apalset EM, Gjesdal CG, Ueland PM, Midttun Ø, Ulvik A, Eide GE, Meyer K and Tell GS: Interferon (IFN)-γ-mediated inflammation and the kynurenine pathway in relation to bone mineral density: The Hordaland health study. Clin Exp Immunol. 176:452–460. 2014. View Article : Google Scholar : PubMed/NCBI | |
Ling CW, Miao Z, Xiao ML, Zhou H, Jiang Z, Fu Y, Xiong F, Zuo LS, Liu YP, Wu YY, et al: The association of gut microbiota with osteoporosis is mediated by amino acid metabolism: Multiomics in a large cohort. J Clin Endocrinol Metab. 106:e3852–e3864. 2021. View Article : Google Scholar : PubMed/NCBI | |
Miyamoto K, Hirayama A, Sato Y, Ikeda S, Maruyama M, Soga T, Tomita M, Nakamura M, Matsumoto M, Yoshimura N and Miyamoto T: A metabolomic profile predictive of new osteoporosis or sarcopenia development. Metabolites. 11:2782021. View Article : Google Scholar : PubMed/NCBI | |
Zhang X, Xu H, Li GH, Long MT, Cheung CL, Vasan RS, Hsu YH, Kiel DP and Liu CT: Metabolomics insights into osteoporosis through association with bone mineral density. J Bone Miner Res. 36:729–738. 2021. View Article : Google Scholar : PubMed/NCBI | |
Eriksson AL, Friedrich N, Karlsson MK, Ljunggren Ö, Lorentzon M, Nethander M, Wallaschofski H, Mellström D and Ohlsson C: Serum glycine levels are associated with cortical bone properties and fracture risk in men. J Clin Endocrinol Metab. 106:e5021–e5029. 2021.PubMed/NCBI | |
Jennings A, MacGregor A, Spector T and Cassidy A: Amino acid intakes are associated with bone mineral density and prevalence of low bone mass in women: Evidence from discordant monozygotic twins. J Bone Miner Res. 31:326–335. 2016. View Article : Google Scholar : PubMed/NCBI | |
Kim MH, Kim HM and Jeong HJ: Estrogen-like osteoprotective effects of glycine in in vitro and in vivo models of menopause. Amino Acids. 48:791–800. 2016. View Article : Google Scholar : PubMed/NCBI | |
Li X, Lin Q, Cui Y, Wang H, Wang P, Yang L, Ye Q, Zhang R and Zhu X: Glycine acts through estrogen receptor alpha to mediate estrogen receptor signaling, stimulating osteogenesis and attenuating adipogenesis in ovariectomized rats. Mol Nutr Food Res. 66:e21008572022. View Article : Google Scholar : PubMed/NCBI | |
Wang J, Yan D, Zhao A, Hou X, Zheng X, Chen P, Bao Y and Jia W, Hu C, Zhang ZL and Jia W: Discovery of potential biomarkers for osteoporosis using LC-MS/MS metabolomic methods. Osteoporos Int. 30:1491–1499. 2019. View Article : Google Scholar : PubMed/NCBI | |
Hu G, Yu Y, Ren Y, Tower RJ, Zhang GF and Karner CM: Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice. EMBO Rep. 25:4515–4541. 2024. View Article : Google Scholar : PubMed/NCBI | |
Lamont LS, McCullough AJ and Kalhan SC: Gender differences in the regulation of amino acid metabolism. J Appl Physiol (1985). 95:1259–1265. 2003. View Article : Google Scholar : PubMed/NCBI | |
Zhang YW, Song PR, Wang SC, Liu H, Shi ZM and Su JC: Diets intervene osteoporosis via gut-bone axis. Gut Microbes. 16:22954322024. View Article : Google Scholar : PubMed/NCBI | |
Mann ER, Lam YK and Uhlig HH: Short-chain fatty acids: Linking diet, the microbiome and immunity. Nat Rev Immunol. 24:577–595. 2024. View Article : Google Scholar : PubMed/NCBI | |
Palacios-González B, Ramírez-Salazar EG, Rivera-Paredez B, Quiterio M, Flores YN, Macias-Kauffer L, Moran-Ramos S, Denova-Gutiérrez E, Ibarra-González I, Vela-Amieva M, et al: A Multi-Omic Analysis for Low Bone Mineral Density in Postmenopausal Women Suggests a RELATIONSHIP between Diet, Metabolites, and Microbiota. Microorganisms. 8:16302020. View Article : Google Scholar : PubMed/NCBI | |
Palacios-González B, León-Reyes G, Rivera-Paredez B, Ibarra-González I, Vela-Amieva M, Flores YN, Canizales-Quinteros S, Salmerón J and Velázquez-Cruz R: Serum metabolite profile associated with sex-dependent visceral adiposity index and low bone mineral density in a mexican population. Metabolites. 11:6042021. View Article : Google Scholar : PubMed/NCBI | |
Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, Li T and Yin Y: Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol. 8:132018. View Article : Google Scholar : PubMed/NCBI | |
Ye Q, Xi X, Fan D, Cao X, Wang Q, Wang X, Zhang M, Wang B, Tao Q, Xiao C, et al: Polycyclic aromatic hydrocarbons in bone homeostasis. Biomed Pharmacother. 146:1125472022. View Article : Google Scholar : PubMed/NCBI | |
Wang L, Wang Z, Luo P, Bai S, Chen Y and Chen W: Dietary zinc glycine supplementation improves tibia quality of meat ducks by modulating the intestinal barrier and bone resorption. Biol Trace Elem Res. 201:888–903. 2023. View Article : Google Scholar : PubMed/NCBI | |
Gao W: Effects of lactobacillus on glucolipids metabolism and intestinal flora in type 2 diabetic mice fed with high-glucose and high-fat diet (master's thesis). Shanxi Normal University; 2018, (In Chinese). | |
Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermúdez-Humarán LG, Smirnova N, Bergé M, Sulpice T, Lahtinen S, et al: Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: Molecular mechanisms and probiotic treatment. EMBO Mol Med. 3:559–572. 2011. View Article : Google Scholar : PubMed/NCBI | |
Imerb N, Thonusin C, Chattipakorn N and Chattipakorn SC: Aging, obese-insulin resistance, and bone remodeling. Mech Ageing Dev. 191:1113352020. View Article : Google Scholar : PubMed/NCBI | |
Lau KT, Krishnamoorthy S, Sing CW and Cheung CL: Metabolomics of osteoporosis in humans: A systematic review. Curr Osteoporos Rep. 21:278–288. 2023. View Article : Google Scholar : PubMed/NCBI | |
Kitaura H, Marahleh A, Ohori F, Noguchi T, Shen WR, Qi J, Nara Y, Pramusita A, Kinjo R and Mizoguchi I: Osteocyte-related cytokines regulate osteoclast formation and bone resorption. Int J Mol Sci. 21:51692020. View Article : Google Scholar : PubMed/NCBI | |
Li R, Kato H, Nakata T, Yamawaki I, Yamauchi N, Imai K, Taguchi Y and Umeda M: Essential amino acid starvation induces cell cycle arrest, autophagy, and inhibits osteogenic differentiation in murine osteoblast. Biochem Biophys Res Commun. 672:168–176. 2023. View Article : Google Scholar : PubMed/NCBI | |
Rong Y, Darnell AM, Sapp KM, Vander Heiden MG and Spencer SL: Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids. Cell Rep. 42:1135392023. View Article : Google Scholar : PubMed/NCBI | |
Li R, Kato H, Fumimoto C, Nakamura Y, Yoshimura K, Minagawa E, Omatsu K, Ogata C, Taguchi Y and Umeda M: Essential amino acid starvation-induced oxidative stress causes DNA damage and apoptosis in murine osteoblast-like cells. Int J Mol Sci. 24:153142023. View Article : Google Scholar : PubMed/NCBI | |
Shen L, Yu Y and Karner CM: SLC38A2 provides proline and alanine to regulate postnatal bone mass accrual in mice. Front Physiol. 13:9926792022. View Article : Google Scholar : PubMed/NCBI | |
Sharma D, Yu Y, Shen L, Zhang GF and Karner CM: SLC1A5 provides glutamine and asparagine necessary for bone development in mice. Elife. 10:e715952021. View Article : Google Scholar : PubMed/NCBI | |
Jiménez JA, Lawlor ER and Lyssiotis CA: Amino acid metabolism in primary bone sarcomas. Front Oncol. 12:10013182022. View Article : Google Scholar : PubMed/NCBI | |
Shen L, Sharma D, Yu Y, Long F and Karner CM: Biphasic regulation of glutamine consumption by WNT during osteoblast differentiation. J Cell Sci. 134:jcs2516452021.PubMed/NCBI | |
Nie C, He T, Zhang W, Zhang G and Ma X: Branched chain amino acids: beyond nutrition metabolism. Int J Mol Sci. 19:9542018. View Article : Google Scholar : PubMed/NCBI | |
Brunner JS, Vulliard L, Hofmann M, Kieler M, Lercher A, Vogel A, Russier M, Brüggenthies JB, Kerndl M, Saferding V, et al: Environmental arginine controls multinuclear giant cell metabolism and formation. Nat Commun. 11:4312020. View Article : Google Scholar : PubMed/NCBI | |
Bordbar A, Mo ML, Nakayasu ES, Schrimpe-Rutledge AC, Kim YM, Metz TO, Jones MB, Frank BC, Smith RD, Peterson SN, et al: Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation. Mol Syst Biol. 8:5582012. View Article : Google Scholar : PubMed/NCBI | |
Onuora S: L-arginine inhibits arthritis and bone loss by reprogramming osteoclast metabolism. Nat Rev Rheumatol. 19:7602023. View Article : Google Scholar : PubMed/NCBI | |
Shen Y, Wang H, Xie H, Zhang J, Ma Q, Wang S, Yuan P, Xue H, Hong H, Fan S, et al: l-arginine promotes angio-osteogenesis to enhance oxidative stress-inhibited bone formation by ameliorating mitophagy. J Orthop Translat. 46:53–64. 2024. View Article : Google Scholar : PubMed/NCBI | |
Stegen S, Moermans K, Stockmans I, Thienpont B and Carmeliet G: The serine synthesis pathway drives osteoclast differentiation through epigenetic regulation of NFATc1 expression. Nat Metab. 6:141–152. 2024. View Article : Google Scholar : PubMed/NCBI | |
Zhou T, Yang Y, Chen Q and Xie L: Glutamine metabolism is essential for stemness of bone marrow mesenchymal stem cells and bone homeostasis. Stem Cells Int. 2019:89289342019. View Article : Google Scholar : PubMed/NCBI | |
Yu Y, Newman H, Shen L, Sharma D, Hu G, Mirando AJ, Zhang H, Knudsen E, Zhang GF, Hilton MJ and Karner CM: Glutamine metabolism regulates proliferation and lineage allocation in skeletal stem cells. Cell Metab. 29:966–978.e4. 2019. View Article : Google Scholar : PubMed/NCBI | |
Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT and Dang CV: c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 458:762–765. 2009. View Article : Google Scholar : PubMed/NCBI | |
Tsumura H, Shindo M, Ito M, Igarashi A, Takeda K, Matsumoto K, Ohkura T, Miyado K, Sugiyama F, Umezawa A and Ito Y: Relationships between Slc1a5 and osteoclastogenesis. Comp Med. 71:285–294. 2021. View Article : Google Scholar : PubMed/NCBI | |
Indo Y, Takeshita S, Ishii KA, Hoshii T, Aburatani H, Hirao A and Ikeda K: Metabolic regulation of osteoclast differentiation and function. J Bone Miner Res. 28:2392–2399. 2013. View Article : Google Scholar : PubMed/NCBI | |
Peng R, Dong Y, Zheng M, Kang H, Wang P, Zhu M, Song K, Wu W and Li F: IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism. Cell Death Dis. 15:1112024. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Wang Z, Duan N, Zhu G, Schwarz EM and Xie C: Osteoblast-osteoclast interactions. Connect Tissue Res. 59:99–107. 2018. View Article : Google Scholar : PubMed/NCBI | |
Zhang W, Dang K, Huai Y and Qian A: Osteoimmunology: The regulatory roles of T lymphocytes in osteoporosis. Front Endocrinol (Lausanne). 11:4652020. View Article : Google Scholar : PubMed/NCBI | |
Mellor AL and Munn DH: IDO expression by dendritic cells: Tolerance and tryptophan catabolism. Nat Rev Immunol. 4:762–774. 2004. View Article : Google Scholar : PubMed/NCBI | |
Zara C, Severino A, Flego D, Ruggio A, Pedicino D, Giglio AF, Trotta F, Lucci C, D'Amario D, Vinci R, et al: Indoleamine 2,3-Dioxygenase (IDO) enzyme links innate immunity and altered T-cell differentiation in Non-ST segment elevation acute coronary syndrome. Int J Mol Sci. 19:632017. View Article : Google Scholar : PubMed/NCBI | |
Eagle H, Oyama VI, Levy M, Horton CL and Fleischman R: The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J Biol Chem. 218:607–616. 1956. View Article : Google Scholar : PubMed/NCBI | |
Colombo SL, Palacios-Callender M, Frakich N, Carcamo S, Kovacs I, Tudzarova S and Moncada S: Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc Natl Acad Sci USA. 108:21069–21074. 2011. View Article : Google Scholar : PubMed/NCBI | |
Ahn E, Kumar P, Mukha D, Tzur A and Shlomi T: Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle. Mol Syst Biol. 13:9532017. View Article : Google Scholar : PubMed/NCBI | |
Malakar P, Singha D, Choudhury D and Shukla S: Glutamine regulates the cellular proliferation and cell cycle progression by modulating the mTOR mediated protein levels of β-TrCP. Cell Cycle. 22:1937–1950. 2023. View Article : Google Scholar : PubMed/NCBI | |
Minchenko DO, Hubenya OV, Terletsky BM, Moenner M and Minchenko OH: Effect of glutamine or glucose deprivation on the expression of cyclin and cyclin-dependent kinase genes in glioma cell line U87 and its subline with suppressed activity of signaling enzyme of endoplasmic reticulum-nuclei-1. Ukr Biokhim Zh (1999). 83:18–29. 2011.PubMed/NCBI | |
Yuan L, Sheng X, Willson AK, Roque DR, Stine JE, Guo H, Jones HM, Zhou C and Bae-Jump VL: Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway. Endocr Relat Cancer. 22:577–591. 2015. View Article : Google Scholar : PubMed/NCBI | |
Kim B, Li J, Jang C and Arany Z: Glutamine fuels proliferation but not migration of endothelial cells. EMBO J. 36:2321–2333. 2017. View Article : Google Scholar : PubMed/NCBI | |
Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, Cao J, Xie N, Velletri T, Zhang X, et al: Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts? Cell Death Differ. 23:1128–1139. 2016. View Article : Google Scholar : PubMed/NCBI | |
Ning K, Liu S, Yang B, Wang R, Man G, Wang DE and Xu H: Update on the effects of energy metabolism in bone marrow mesenchymal stem cells differentiation. Mol Metab. 58:1014502022. View Article : Google Scholar : PubMed/NCBI | |
Skerry TM: The role of glutamate in the regulation of bone mass and architecture. J Musculoskelet Neuronal Interact. 8:166–173. 2008.PubMed/NCBI | |
Wang Y, Deng P, Liu Y, Wu Y, Chen Y, Guo Y, Zhang S, Zheng X, Zhou L, Liu W, et al: Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nat Commun. 11:55962020. View Article : Google Scholar : PubMed/NCBI | |
Fan M, Shi H, Yao H, Wang W, Zhang Y, Jiang C and Lin R: Glutamate regulates gliosis of BMSCs to promote ENS regeneration through α-KG and H3K9/H3K27 demethylation. Stem Cell Res Ther. 13:2552022. View Article : Google Scholar : PubMed/NCBI | |
Qian D, Wei G, Xu C, He Z, Hua J, Li J, Hu Q, Lin S, Gong J, Meng H, et al: Bone marrow-derived mesenchymal stem cells (BMSCs) repair acute necrotized pancreatitis by secreting microRNA-9 to target the NF-κB1/p50 gene in rats. Sci Rep. 7:5812017. View Article : Google Scholar : PubMed/NCBI | |
Ganesan R and 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. Mol Immunol. 91:134–144. 2017. View Article : Google Scholar : PubMed/NCBI | |
Saraiva M, Vieira P and O'Garra A: Biology and therapeutic potential of interleukin-10. J Exp Med. 217:e201904182020. View Article : Google Scholar : PubMed/NCBI | |
Mielle J, Morel J, Elhmioui J, Combe B, Macia L, Dardalhon V, Taylor N, Audo R and Daien C: Glutamine promotes the generation of B10+ cells via the mTOR/GSK3 pathway. Eur J Immunol. 52:418–430. 2022. View Article : Google Scholar : PubMed/NCBI | |
Liu JQ, Geng XR, Hu TY, Mo LH, Luo XQ, Qiu SY, Liu DB, Liu ZG, Shao JB, Liu ZQ and Yang PC: Glutaminolysis is required in maintaining immune regulatory functions in B cells. Mucosal Immunol. 15:268–278. 2022. View Article : Google Scholar : PubMed/NCBI | |
Coëffier M, Marion R, Ducrotté P and Déchelotte P: Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut. Clin Nutr. 22:407–413. 2003. View Article : Google Scholar : PubMed/NCBI | |
Santos AC, Correia CA, de Oliveira DC, Nogueira-Pedro A, Borelli P and Fock RA: Intravenous glutamine administration modulates TNF-α/IL-10 ratio and attenuates NFkB phosphorylation in a protein malnutrition model. Inflammation. 39:1883–1891. 2016. View Article : Google Scholar : PubMed/NCBI | |
da Silva Lima F, Rogero MM, Ramos MC, Borelli P and Fock RA: Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition. Eur J Nutr. 52:1343–1351. 2013. View Article : Google Scholar : PubMed/NCBI | |
Sun Y, Ma J, Li D, Li P, Zhou X, Li Y, He Z, Qin L, Liang L and Luo X: Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures. J Neuroinflammation. 16:662019. View Article : Google Scholar : PubMed/NCBI | |
Levy DE and Lee CK: What does Stat3 do? J Clin Invest. 109:1143–1148. 2002. View Article : Google Scholar : PubMed/NCBI | |
Dos Santos GG, Hastreiter AA, Sartori T, Borelli P and Fock RA: L-Glutamine in vitro modulates some immunomodulatory properties of bone marrow mesenchymal stem cells. Stem Cell Rev Rep. 13:482–490. 2017. View Article : Google Scholar : PubMed/NCBI | |
Refaey ME, McGee-Lawrence ME, Fulzele S, Kennedy EJ, Bollag WB, Elsalanty M, Zhong Q, Ding KH, Bendzunas NG, Shi XM, et al: Kynurenine, a tryptophan metabolite that accumulates with age, induces bone loss. J Bone Miner Res. 32:2182–2193. 2017. View Article : Google Scholar : PubMed/NCBI | |
Dalton S, Smith K, Singh K, Kaiser H, Kolhe R, Mondal AK, Khayrullin A, Isales CM, Hamrick MW, Hill WD and Fulzele S: Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells. Exp Gerontol. 130:1108002020. View Article : Google Scholar : PubMed/NCBI | |
Sas K, Szabó E and Vécsei L: Mitochondria, oxidative stress and the kynurenine system, with a focus on ageing and neuroprotection. Molecules. 23:1912018. View Article : Google Scholar : PubMed/NCBI | |
Elmansi AM, Hussein KA, Herrero SM, Periyasamy-Thandavan S, Aguilar-Pérez A, Kondrikova G, Kondrikov D, Eisa NH, Pierce JL, Kaiser H, et al: Age-related increase of kynurenine enhances miR29b-1-5p to decrease both CXCL12 signaling and the epigenetic enzyme Hdac3 in bone marrow stromal cells. Bone Rep. 12:1002702020. View Article : Google Scholar : PubMed/NCBI | |
Kondrikov D, Elmansi A, Bragg RT, Mobley T, Barrett T, Eisa N, Kondrikova G, Schoeinlein P, Aguilar-Perez A, Shi XM, et al: Kynurenine inhibits autophagy and promotes senescence in aged bone marrow mesenchymal stem cells through the aryl hydrocarbon receptor pathway. Exp Gerontol. 130:1108052020. View Article : Google Scholar : PubMed/NCBI | |
Anaya JM, Bollag WB, Hamrick MW and Isales CM: The role of tryptophan metabolites in musculoskeletal stem cell aging. Int J Mol Sci. 21:66702020. View Article : Google Scholar : PubMed/NCBI | |
Sautchuk R Jr and Eliseev RA: Cell energy metabolism and bone formation. Bone Rep. 16:1015942022. View Article : Google Scholar : PubMed/NCBI | |
Li S, Tian Q, Zheng L and Zhou Y: Functional amino acids in the regulation of bone and its diseases. Mol Nutr Food Res. 68:e24000942024. View Article : Google Scholar : PubMed/NCBI | |
Ledesma-Colunga MG, Passin V, Lademann F, Hofbauer LC and Rauner M: Novel insights into osteoclast energy metabolism. Curr Osteoporos Rep. 21:660–669. 2023. View Article : Google Scholar : PubMed/NCBI | |
Carbone L, Bůžková P, Fink HA, Robbins JA, Barzilay JI, Elam RE, Isales C, Connelly MA and Mukamal KJ: Plasma levels of branched chain amino acids, incident hip fractures, and bone mineral density of the hip and spine. J Clin Endocrinol Metab. 108:e1358–e1364. 2023. View Article : Google Scholar : PubMed/NCBI | |
Su Y, Elshorbagy A, Turner C, Refsum H, Chan R and Kwok T: Circulating amino acids are associated with bone mineral density decline and ten-year major osteoporotic fracture risk in older community-dwelling adults. Bone. 129:1150822019. View Article : Google Scholar : PubMed/NCBI | |
Liang B, Shi X, Wang X, Ma C, Leslie WD, Lix LM, Shi X, Kan B and Yang S: Association between amino acids and recent osteoporotic fracture: A matched incident case-control study. Front Nutr. 11:13609592024. View Article : Google Scholar : PubMed/NCBI | |
Zhang YY, Xie N, Sun XD, Nice EC, Liou YC, Huang C, Zhu H and Shen Z: Insights and implications of sexual dimorphism in osteoporosis. Bone Res. 12:82024. View Article : Google Scholar : PubMed/NCBI | |
Guan Z, Luo L, Liu S, Guan Z, Zhang Q, Li X and Tao K: The role of depletion of gut microbiota in osteoporosis and osteoarthritis: A narrative review. Front Endocrinol (Lausanne). 13:8474012022. View Article : Google Scholar : PubMed/NCBI | |
Hao L, Yan Y, Huang G and Li H: From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management. Front Cell Infect Microbiol. 14:14167392024. View Article : Google Scholar : PubMed/NCBI |