{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:26:02Z","timestamp":1786123562958,"version":"build-2736575974"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation Flanders","doi-asserted-by":"publisher","award":["G0C5120N"],"award-info":[{"award-number":["G0C5120N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["STG\/22\/034"],"award-info":[{"award-number":["STG\/22\/034"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C24M\/22\/058"],"award-info":[{"award-number":["C24M\/22\/058"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bone"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.bone.2026.117980","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:38:29Z","timestamp":1781627909000},"page":"117980","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Metabolic flexibility secures skeletal progenitor function upon reduced glycolysis driven by PFKFB3 loss"],"prefix":"10.1016","volume":"211","author":[{"given":"Lore","family":"Rosseels","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Stockmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Moermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Blockx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter-Jan","family":"Coolen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan I.","family":"Dmitriev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Carmeliet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Carmeliet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Stegen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bone.2026.117980_bb0005","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41574-024-00969-x","article-title":"Metabolic regulation of skeletal cell fate and function","volume":"20","author":"Stegen","year":"2024","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.bone.2026.117980_bb0010","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s42255-020-00321-3","article-title":"Metabolic regulation of skeletal cell fate and function in physiology and disease","volume":"3","author":"van Gastel","year":"2021","journal-title":"Nat. Metab."},{"key":"10.1016\/j.bone.2026.117980_bb0015","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bone.2014.08.007","article-title":"Uncovering the periosteum for skeletal regeneration: the stem cell that lies beneath","volume":"70","author":"Roberts","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.bone.2026.117980_bb0020","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fcell.2019.00189","article-title":"A revised perspective of skeletal stem cell biology","volume":"7","author":"Ambrosi","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.bone.2026.117980_bb0025","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3389\/fcell.2020.00592","article-title":"Niches for skeletal stem cells of mesenchymal origin","volume":"8","author":"Kurenkova","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.bone.2026.117980_bb0030","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41574-024-01039-y","article-title":"Skeletal stem and progenitor cells in bone physiology, ageing and disease","volume":"21","author":"Melis","year":"2025","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.bone.2026.117980_bb0035","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.cmet.2019.01.016","article-title":"Glutamine metabolism regulates proliferation and lineage allocation in skeletal stem cells","volume":"29","author":"Yu","year":"2019","journal-title":"Cell Metab."},{"key":"10.1016\/j.bone.2026.117980_bb0040","article-title":"Amino acid metabolism in skeletal cells","volume":"17","author":"Devignes","year":"2022","journal-title":"Bone Rep."},{"key":"10.1016\/j.bone.2026.117980_bb0045","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41586-020-2050-1","article-title":"Lipid availability determines fate of skeletal progenitor cells via SOX9","volume":"579","author":"van Gastel","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.bone.2026.117980_bb0050","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bone.2017.08.008","article-title":"Glucose metabolism in bone","volume":"115","author":"Karner","year":"2018","journal-title":"Bone"},{"key":"10.1016\/j.bone.2026.117980_bb0055","doi-asserted-by":"crossref","DOI":"10.1038\/s41574-025-01162-4","article-title":"The role of bone in whole-body energy metabolism","author":"Lecka-Czernik","year":"2025","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.bone.2026.117980_bb0060","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/jbmr\/zjad016","article-title":"Hypoxia rewires glucose and glutamine metabolism in different sources of skeletal stem and progenitor cells similarly, except for pyruvate","volume":"39","author":"Loopmans","year":"2024","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2026.117980_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2022.101635","article-title":"Monitoring and modelling the dynamics of the cellular glycolysis pathway: a review and future perspectives","volume":"66","author":"Patil","year":"2022","journal-title":"Mol. Metab."},{"key":"10.1016\/j.bone.2026.117980_bb0070","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1073\/pnas.78.6.3483","article-title":"Control of liver 6-phosphofructokinase by fructose 2,6-bisphosphate and other effectors","volume":"78","author":"Van Schaftingen","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bone.2026.117980_bb0075","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0968-0004(00)01699-6","article-title":"PFK-2\/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate","volume":"26","author":"Okar","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.bone.2026.117980_bb0080","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1074\/jbc.M511019200","article-title":"Crystal structure of the hypoxia-inducible form of 6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase (PFKFB3): a possible new target for cancer therapy","volume":"281","author":"Kim","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bone.2026.117980_bb0085","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/oxfordjournals.jbchem.a021719","article-title":"Characterization of a human placental fructose-6-phosphate, 2-kinase\/fructose-2,6-bisphosphatase","volume":"122","author":"Sakakibara","year":"1997","journal-title":"J. Biochem."},{"key":"10.1016\/j.bone.2026.117980_bb0090","doi-asserted-by":"crossref","first-page":"17044","DOI":"10.1038\/sigtrans.2017.44","article-title":"Roles of PFKFB3 in cancer","volume":"2","author":"Shi","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bone.2026.117980_bb0095","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13040909","article-title":"Role of PFKFB3 and PFKFB4 in cancer: genetic basis, impact on disease development\/progression, and potential as therapeutic targets","volume":"13","author":"Kotowski","year":"2021","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.bone.2026.117980_bb0100","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s10456-017-9573-6","article-title":"Tumor vessel disintegration by maximum tolerable PFKFB3 blockade","volume":"20","author":"Conradi","year":"2017","journal-title":"Angiogenesis"},{"key":"10.1016\/j.bone.2026.117980_bb0105","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cmet.2013.11.008","article-title":"Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis","volume":"19","author":"Schoors","year":"2014","journal-title":"Cell Metab."},{"key":"10.1016\/j.bone.2026.117980_bb0110","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.cell.2013.06.037","article-title":"Role of PFKFB3-driven glycolysis in vessel sprouting","volume":"154","author":"De Bock","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.bone.2026.117980_bb0115","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.ccell.2016.10.006","article-title":"Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy","volume":"30","author":"Cantelmo","year":"2016","journal-title":"Cancer Cell"},{"key":"10.1016\/j.bone.2026.117980_bb0120","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.4049\/jimmunol.1600474","article-title":"PFKFB3-driven macrophage glycolytic metabolism is a crucial component of innate antiviral defense","volume":"197","author":"Jiang","year":"2016","journal-title":"J. Immunol."},{"key":"10.1016\/j.bone.2026.117980_bb0125","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/gene.10092","article-title":"Expression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer","volume":"33","author":"Logan","year":"2002","journal-title":"Genesis"},{"key":"10.1016\/j.bone.2026.117980_bb0130","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.930358","article-title":"Isolation and in vitro characterization of murine young-adult long bone skeletal progenitors","volume":"13","author":"Loopmans","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"10.1016\/j.bone.2026.117980_bb0135","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41586-019-0874-3","article-title":"HIF-1alpha metabolically controls collagen synthesis and modification in chondrocytes","volume":"565","author":"Stegen","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.bone.2026.117980_bb0140","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/jbmr.4219","article-title":"Glutamine metabolism in osteoprogenitors is required for bone mass accrual and PTH-induced bone anabolism in male mice","volume":"36","author":"Stegen","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2026.117980_bb0145","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41413-021-00185-7","article-title":"De novo serine synthesis regulates chondrocyte proliferation during bone development and repair","volume":"10","author":"Stegen","year":"2022","journal-title":"Bone Res."},{"key":"10.1016\/j.bone.2026.117980_bb0150","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1002\/stem.1210","article-title":"Engineering vascularized bone: osteogenic and proangiogenic potential of murine periosteal cells","volume":"30","author":"van Gastel","year":"2012","journal-title":"Stem Cells"},{"key":"10.1016\/j.bone.2026.117980_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2020.115259","article-title":"Nestin-GFP transgene labels skeletal progenitors in the periosteum","volume":"133","author":"Tournaire","year":"2020","journal-title":"Bone"},{"key":"10.1016\/j.bone.2026.117980_bb0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111105","article-title":"Skeletal progenitors preserve proliferation and self-renewal upon inhibition of mitochondrial respiration by rerouting the TCA cycle","volume":"40","author":"Tournaire","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.bone.2026.117980_bb0165","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.devcel.2020.05.001","article-title":"Glutamine metabolism controls chondrocyte identity and function","volume":"53","author":"Stegen","year":"2020","journal-title":"Dev. Cell"},{"key":"10.1016\/j.bone.2026.117980_bb0170","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.stem.2017.02.009","article-title":"Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration","volume":"20","author":"Ambrosi","year":"2017","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.bone.2026.117980_bb0175","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s42255-023-00948-y","article-title":"The serine synthesis pathway drives osteoclast differentiation through epigenetic regulation of NFATc1 expression","volume":"6","author":"Stegen","year":"2024","journal-title":"Nat. Metab."},{"key":"10.1016\/j.bone.2026.117980_bb0180","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1007\/s00198-020-05438-5","article-title":"Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography","volume":"31","author":"Whittier","year":"2020","journal-title":"Osteoporos. Int."},{"key":"10.1016\/j.bone.2026.117980_bb0185","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/jbmr.1805","article-title":"Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee","volume":"28","author":"Dempster","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2026.117980_bb0190","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1002\/jbmr.2714","article-title":"PTH promotes bone anabolism by stimulating aerobic glycolysis via IGF signaling","volume":"30","author":"Esen","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2026.117980_bb0195","doi-asserted-by":"crossref","first-page":"8673","DOI":"10.1073\/pnas.1324290111","article-title":"Up-regulation of glycolytic metabolism is required for HIF1alpha-driven bone formation","volume":"111","author":"Regan","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bone.2026.117980_bb0200","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.182330","article-title":"HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation","volume":"9","author":"Khan","year":"2024","journal-title":"JCI Insight"},{"key":"10.1016\/j.bone.2026.117980_bb0205","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bone.2017.08.022","article-title":"The skeletal vascular system \u2014 breathing life into bone tissue","volume":"115","author":"Stegen","year":"2018","journal-title":"Bone"},{"key":"10.1016\/j.bone.2026.117980_bb0210","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cmet.2016.01.002","article-title":"HIF-1alpha promotes glutamine-mediated redox homeostasis and glycogen-dependent bioenergetics to support postimplantation bone cell survival","volume":"23","author":"Stegen","year":"2016","journal-title":"Cell Metab."},{"key":"10.1016\/j.bone.2026.117980_bb0215","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.bone.2016.03.014","article-title":"Adequate hypoxia inducible factor 1alpha signaling is indispensable for bone regeneration","volume":"87","author":"Stegen","year":"2016","journal-title":"Bone"},{"key":"10.1016\/j.bone.2026.117980_bb0220","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.devcel.2019.04.029","article-title":"Suppressing mitochondrial respiration is critical for hypoxia tolerance in the fetal growth plate","volume":"49","author":"Yao","year":"2019","journal-title":"Dev. Cell"},{"key":"10.1016\/j.bone.2026.117980_bb0225","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1097\/MNH.0000000000000508","article-title":"Hypoxia, hypoxia-inducible transcription factors and oxygen-sensing prolyl hydroxylases in bone development and homeostasis","volume":"28","author":"Stegen","year":"2019","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"10.1016\/j.bone.2026.117980_bb0230","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.devcel.2021.03.007","article-title":"BCKDK regulates the TCA cycle through PDC in the absence of PDK family during embryonic development","volume":"56","author":"Heinemann-Yerushalmi","year":"2021","journal-title":"Dev. Cell"},{"key":"10.1016\/j.bone.2026.117980_bb0235","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.76963","article-title":"SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation","volume":"11","author":"Shen","year":"2022","journal-title":"Elife"},{"key":"10.1016\/j.bone.2026.117980_bb0240","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.992679","article-title":"SLC38A2 provides proline and alanine to regulate postnatal bone mass accrual in mice","volume":"13","author":"Shen","year":"2022","journal-title":"Front. Physiol."},{"key":"10.1016\/j.bone.2026.117980_bb0245","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bone.2014.09.017","article-title":"Bringing new life to damaged bone: the importance of angiogenesis in bone repair and regeneration","volume":"70","author":"Stegen","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.bone.2026.117980_bb0250","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.chembiol.2023.07.003","article-title":"Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes","volume":"30","author":"Ji","year":"2023","journal-title":"Cell Chem. Biol."}],"container-title":["Bone"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328226002061?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328226002061?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:41:35Z","timestamp":1786117295000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S8756328226002061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":50,"alternative-id":["S8756328226002061"],"URL":"https:\/\/doi.org\/10.1016\/j.bone.2026.117980","relation":{},"ISSN":["8756-3282"],"issn-type":[{"value":"8756-3282","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Metabolic flexibility secures skeletal progenitor function upon reduced glycolysis driven by PFKFB3 loss","name":"articletitle","label":"Article Title"},{"value":"Bone","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bone.2026.117980","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117980"}}