{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T08:30:47Z","timestamp":1780389047836,"version":"3.54.1"},"reference-count":104,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0B5219N"],"award-info":[{"award-number":["G0B5219N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1291522N"],"award-info":[{"award-number":["1291522N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S03417N"],"award-info":[{"award-number":["1S03417N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1291522N"],"award-info":[{"award-number":["1291522N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S03417N"],"award-info":[{"award-number":["1S03417N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bone Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Obesity and type-2 diabetes, two interconnected and increasingly prevalent metabolic disorders, are associated with poor bone quality, higher fracture risk, and impaired fracture repair. The causes are not yet resolved but appear to relate to the impaired glucose homeostasis, altered bone material properties and remodeling, and compromised skeletal vascularization. Each of these features is impacted by hypoxia-inducible factor (HIF) signaling, which led us to hypothesize that HIF pathway modulation might be an effective strategy to concomitantly improve energy metabolism and bone health in conditions of metabolic stress. Here, we evaluated whether pharmacological HIF activation using the HIF-prolyl-hydroxylase-domain enzyme (PHD) inhibitor FG-4592 (Roxadustat) could protect mice against the adverse skeletal and metabolic consequences of high-fat diet (HFD)-induced obesity. We found that systemic FG-4592 treatment effectively prevented HFD-triggered body weight gain, glucose intolerance, and peripheral fat accumulation, associated with globally increased energy expenditure. Concomitantly, FG-4592 administration prevented the skeletal vascular damage, marrow fat accumulation, and bone formation deficits that were caused by HFD. Moreover, the HIF-activating drug also improved glucose metabolism and bone regeneration in a model of compromised fracture repair associated with overnutrition. Specifically, short-term FG-4592 treatment during fracture recovery reduced the body weight and fat mass of obese mice, improved glucose tolerance, and enhanced the fracture bridging capacity, along with promoting callus vascularization. These findings demonstrate that systemic hypoxia signaling stimulation using PHD inhibitors alleviates both the metabolic and skeletal consequences of diet-induced obesity in mice, highlighting its potential as a dual-action therapeutic strategy for enhancing glucose homeostasis and bone health\/regeneration in disorders of obesity and metabolic dysfunction.<\/jats:p>","DOI":"10.1038\/s41413-025-00503-3","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T03:52:38Z","timestamp":1770781958000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacological HIF activation protects against diet-induced obesity, glucose intolerance, and skeletal dysfunction by exerting dual beneficial effects on energy metabolism and bone"],"prefix":"10.1038","volume":"14","author":[{"given":"Roger","family":"Valle-Tenney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-3700","authenticated-orcid":false,"given":"Nicolas","family":"Peredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"De Samblancx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Nefyodova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Cardoen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Dehaemers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Farlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Chapurlat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Van der Schueren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Mathieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3523-669X","authenticated-orcid":false,"given":"Roman","family":"Vangoitsenhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4243-5486","authenticated-orcid":false,"given":"Christa","family":"Maes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"503_CR1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.21037\/atm.2017.03.107","volume":"5","author":"M Abdelaal","year":"2017","unstructured":"Abdelaal, M., le Roux, C. W. & Docherty, N. G. Morbidity and mortality associated with obesity. Ann. Transl. Med. 5, 161 (2017).","journal-title":"Ann. Transl. Med."},{"key":"503_CR2","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.3390\/ijms25031882","volume":"25","author":"P Chandrasekaran","year":"2024","unstructured":"Chandrasekaran, P. & Weiskirchen, R. The role of obesity in type 2 diabetes mellitus\u2014an overview. Int J. Mol. Sci. 25, 1882 (2024).","journal-title":"Int J. Mol. Sci."},{"key":"503_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1161521","volume":"14","author":"R Ruze","year":"2023","unstructured":"Ruze, R. et al. Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. Front. Endocrinol. 14, 1161521 (2023).","journal-title":"Front. Endocrinol."},{"key":"503_CR4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cmet.2021.12.012","volume":"34","author":"S Klein","year":"2022","unstructured":"Klein, S., Gastaldelli, A., Yki-Jarvinen, H. & Scherer, P. E. Why does obesity cause diabetes?. Cell Metab. 34, 11\u201320 (2022).","journal-title":"Cell Metab."},{"key":"503_CR5","unstructured":"WHO. WHO World health statistics 2024: monitoring health for the SDGs, Sustainable Development Goals. https:\/\/iris.who.int\/bitstream\/handle\/10665\/376869\/9789240094703-eng.pdf?sequence=1 (2024)."},{"key":"503_CR6","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/S2213-8587(24)00163-3","volume":"12","author":"J Paccou","year":"2024","unstructured":"Paccou, J. & Compston, J. E. Bone health in adults with obesity before and after interventions to promote weight loss. Lancet Diab. Endocrinol. 12, 748\u2013760 (2024).","journal-title":"Lancet Diab. Endocrinol."},{"key":"503_CR7","doi-asserted-by":"publisher","first-page":"e466","DOI":"10.1210\/clinem\/dgad415","volume":"109","author":"R Chen","year":"2024","unstructured":"Chen, R. & Armamento-Villareal, R. Obesity and skeletal fragility. J. Clin. Endocrinol. Metab. 109, e466\u2013e477 (2024).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"503_CR8","doi-asserted-by":"publisher","first-page":"8303","DOI":"10.3390\/ijms23158303","volume":"23","author":"A Pinar-Gutierrez","year":"2022","unstructured":"Pinar-Gutierrez, A., Garcia-Fontana, C., Garcia-Fontana, B. & Munoz-Torres, M. Obesity and bone health: a complex relationship. Int. J. Mol. Sci. 23, 8303 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"503_CR9","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s00198-023-06991-5","volume":"35","author":"GC Guimaraes","year":"2024","unstructured":"Guimaraes, G. C. et al. Obesity, diabetes and risk of bone fragility: How BMAT behavior is affected by metabolic disturbances and its influence on bone health. Osteoporos. Int. 35, 575\u2013588 (2024).","journal-title":"Osteoporos. Int."},{"key":"503_CR10","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.injury.2017.11.006","volume":"49","author":"H Gortler","year":"2018","unstructured":"Gortler, H. et al. Diabetes and healing outcomes in lower extremity fractures: a systematic review. Injury 49, 177\u2013183 (2018).","journal-title":"Injury"},{"key":"503_CR11","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.2337\/db16-0063","volume":"65","author":"DE Sellmeyer","year":"2016","unstructured":"Sellmeyer, D. E. et al. Skeletal metabolism, fracture risk, and fracture outcomes in type 1 and type 2 diabetes. Diabetes 65, 1757\u20131766 (2016).","journal-title":"Diabetes"},{"key":"503_CR12","doi-asserted-by":"publisher","first-page":"13662","DOI":"10.3390\/ijms222413662","volume":"22","author":"G Rinonapoli","year":"2021","unstructured":"Rinonapoli, G. et al. Obesity and bone: a complex relationship. Int. J. Mol. Sci. 22, 13662 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"503_CR13","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.injury.2020.11.029","volume":"52","author":"JA Nicholson","year":"2021","unstructured":"Nicholson, J. A., Makaram, N., Simpson, A. & Keating, J. F. Fracture nonunion in long bones: a literature review of risk factors and surgical management. Injury 52, S3\u2013S11 (2021).","journal-title":"Injury"},{"key":"503_CR14","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135236","volume":"5","author":"BA Eckhardt","year":"2020","unstructured":"Eckhardt, B. A. et al. Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes. JCI Insight 5, e135236 (2020).","journal-title":"JCI Insight"},{"key":"503_CR15","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13493","volume":"23","author":"Z Zhang","year":"2022","unstructured":"Zhang, Z. et al. How high-fat diet affects bone in mice: a systematic review and meta-analysis. Obes. Rev. 23, e13493 (2022).","journal-title":"Obes. Rev."},{"key":"503_CR16","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1007\/s00125-019-4865-6","volume":"62","author":"G Mangialardi","year":"2019","unstructured":"Mangialardi, G. et al. Bone marrow pericyte dysfunction in individuals with type 2 diabetes. Diabetologia 62, 1275\u20131290 (2019).","journal-title":"Diabetologia"},{"key":"503_CR17","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag2809","volume":"9","author":"R Tevlin","year":"2017","unstructured":"Tevlin, R. et al. Pharmacological rescue of diabetic skeletal stem cell niches. Sci. Transl. Med. 9, eaag2809 (2017).","journal-title":"Sci. Transl. Med."},{"key":"503_CR18","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41574-024-01039-y","volume":"21","author":"S Melis","year":"2025","unstructured":"Melis, S., Trompet, D., Chagin, A. S. & Maes, C. Skeletal stem and progenitor cells in bone physiology, ageing and disease. Nat. Rev. Endocrinol. 21, 135\u2013153 (2025).","journal-title":"Nat. Rev. Endocrinol."},{"key":"503_CR19","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1093\/stmcls\/sxab011","volume":"40","author":"F Figeac","year":"2022","unstructured":"Figeac, F. et al. Impaired bone fracture healing in type 2 diabetes is caused by defective functions of skeletal progenitor cells. Stem Cells 40, 149\u2013164 (2022).","journal-title":"Stem Cells"},{"key":"503_CR20","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/s41574-023-00879-4","volume":"19","author":"CJ Rosen","year":"2023","unstructured":"Rosen, C. J. & Horowitz, M. C. Nutrient regulation of bone marrow adipose tissue: skeletal implications of weight loss. Nat. Rev. Endocrinol. 19, 626\u2013638 (2023).","journal-title":"Nat. Rev. Endocrinol."},{"key":"503_CR21","doi-asserted-by":"publisher","first-page":"e99656","DOI":"10.1371\/journal.pone.0099656","volume":"9","author":"ML Brown","year":"2014","unstructured":"Brown, M. L. et al. Delayed fracture healing and increased callus adiposity in a C57BL\/6J murine model of obesity-associated type 2 diabetes mellitus. PLoS ONE 9, e99656 (2014).","journal-title":"PLoS ONE"},{"key":"503_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116008","volume":"150","author":"C Marin","year":"2021","unstructured":"Marin, C., Tuts, J., Luyten, F. P., Vandamme, K. & Kerckhofs, G. Impaired soft and hard callus formation during fracture healing in diet-induced obese mice as revealed by 3D contrast-enhanced computed tomography imaging. Bone 150, 116008 (2021).","journal-title":"Bone"},{"key":"503_CR23","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1016\/j.celrep.2019.04.066","volume":"27","author":"M Tencerova","year":"2019","unstructured":"Tencerova, M. et al. Obesity-associated hypermetabolism and accelerated senescence of bone marrow stromal stem cells suggest a potential mechanism for bone fragility. Cell Rep. 27, 2050\u20132062.e6 (2019).","journal-title":"Cell Rep."},{"key":"503_CR24","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s11010-009-0344-6","volume":"338","author":"W Wang","year":"2010","unstructured":"Wang, W., Zhang, X., Zheng, J. & Yang, J. High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP\/protein kinase A\/extracellular signal-regulated kinase pathway. Mol. Cell. Biochem. 338, 115\u2013122 (2010).","journal-title":"Mol. Cell. Biochem."},{"key":"503_CR25","doi-asserted-by":"publisher","first-page":"11410","DOI":"10.1074\/jbc.M113.541458","volume":"289","author":"A Wang","year":"2014","unstructured":"Wang, A., Midura, R. J., Vasanji, A., Wang, A. J. & Hascall, V. C. Hyperglycemia diverts dividing osteoblastic precursor cells to an adipogenic pathway and induces synthesis of a hyaluronan matrix that is adhesive for monocytes. J. Biol. Chem. 289, 11410\u201311420 (2014).","journal-title":"J. Biol. Chem."},{"key":"503_CR26","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1002\/jbmr.3408","volume":"33","author":"M Tencerova","year":"2018","unstructured":"Tencerova, M. et al. High-fat diet-induced obesity promotes expansion of bone marrow adipose tissue and impairs skeletal stem cell functions in mice. J. Bone Min. Res. 33, 1154\u20131165 (2018).","journal-title":"J. Bone Min. Res."},{"key":"503_CR27","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41574-021-00555-5","volume":"17","author":"S Khosla","year":"2021","unstructured":"Khosla, S., Samakkarnthai, P., Monroe, D. G. & Farr, J. N. Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus. Nat. Rev. Endocrinol. 17, 685\u2013697 (2021).","journal-title":"Nat. Rev. Endocrinol."},{"key":"503_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2022.116485","volume":"163","author":"TL Willett","year":"2022","unstructured":"Willett, T. L., Voziyan, P. & Nyman, J. S. Causative or associative: a critical review of the role of advanced glycation end-products in bone fragility. Bone 163, 116485 (2022).","journal-title":"Bone"},{"key":"503_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115436","volume":"137","author":"DK Khajuria","year":"2020","unstructured":"Khajuria, D. K. et al. Aberrant structure of fibrillar collagen and elevated levels of advanced glycation end products typify delayed fracture healing in the diet-induced obesity mouse model. Bone 137, 115436 (2020).","journal-title":"Bone"},{"key":"503_CR30","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1210\/endrev\/bnaa025","volume":"42","author":"WB Horton","year":"2021","unstructured":"Horton, W. B. & Barrett, E. J. Microvascular dysfunction in diabetes mellitus and cardiometabolic disease. Endocr. Rev. 42, 29\u201355 (2021).","journal-title":"Endocr. Rev."},{"key":"503_CR31","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S2213-8587(21)00347-8","volume":"10","author":"LC Hofbauer","year":"2022","unstructured":"Hofbauer, L. C. et al. Bone fragility in diabetes: novel concepts and clinical implications. Lancet Diab. Endocrinol. 10, 207\u2013220 (2022).","journal-title":"Lancet Diab. Endocrinol."},{"key":"503_CR32","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1038\/nrendo.2016.153","volume":"13","author":"N Napoli","year":"2017","unstructured":"Napoli, N. et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat. Rev. Endocrinol. 13, 208\u2013219 (2017).","journal-title":"Nat. Rev. Endocrinol."},{"key":"503_CR33","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00125-021-05380-z","volume":"64","author":"SB Catrina","year":"2021","unstructured":"Catrina, S. B. & Zheng, X. Hypoxia and hypoxia-inducible factors in diabetes and its complications. Diabetologia 64, 709\u2013716 (2021).","journal-title":"Diabetologia"},{"key":"503_CR34","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41581-019-0182-z","volume":"15","author":"J Schodel","year":"2019","unstructured":"Schodel, J. & Ratcliffe, P. J. Mechanisms of hypoxia signalling: new implications for nephrology. Nat. Rev. Nephrol. 15, 641\u2013659 (2019).","journal-title":"Nat. Rev. Nephrol."},{"key":"503_CR35","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1146\/annurev-pharmtox-010818-021637","volume":"59","author":"GL Semenza","year":"2019","unstructured":"Semenza, G. L. Pharmacologic targeting of hypoxia-inducible factors. Annu. Rev. Pharmacol. Toxicol. 59, 379\u2013403 (2019).","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"503_CR36","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s00223-012-9689-z","volume":"92","author":"C Maes","year":"2013","unstructured":"Maes, C. Role and regulation of vascularization processes in endochondral bones. Calcif. Tissue Int. 92, 307\u2013323 (2013).","journal-title":"Calcif. Tissue Int."},{"key":"503_CR37","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s41584-021-00682-3","volume":"17","author":"J Tuckermann","year":"2021","unstructured":"Tuckermann, J. & Adams, R. H. The endothelium-bone axis in development, homeostasis and bone and joint disease. Nat. Rev. Rheumatol. 17, 608\u2013620 (2021).","journal-title":"Nat. Rev. Rheumatol."},{"key":"503_CR38","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1359\/jbmr.090602","volume":"24","author":"E Schipani","year":"2009","unstructured":"Schipani, E., Maes, C., Carmeliet, G. & Semenza, G. L. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J. Bone Min. Res. 24, 1347\u20131353 (2009).","journal-title":"J. Bone Min. Res."},{"key":"503_CR39","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/nrrheum.2012.36","volume":"8","author":"C Maes","year":"2012","unstructured":"Maes, C., Carmeliet, G. & Schipani, E. Hypoxia-driven pathways in bone development, regeneration and disease. Nat. Rev. Rheumatol. 8, 358\u2013366 (2012).","journal-title":"Nat. Rev. Rheumatol."},{"key":"503_CR40","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1101\/gad.934301","volume":"15","author":"E Schipani","year":"2001","unstructured":"Schipani, E. et al. Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev. 15, 2865\u20132876 (2001).","journal-title":"Genes Dev."},{"key":"503_CR41","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1002\/jbmr.1487","volume":"27","author":"C Maes","year":"2012","unstructured":"Maes, C. et al. VEGF-independent cell-autonomous functions of HIF-1alpha regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival. J. Bone Min. Res. 27, 596\u2013609 (2012).","journal-title":"J. Bone Min. Res."},{"key":"503_CR42","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/9467","volume":"5","author":"HP Gerber","year":"1999","unstructured":"Gerber, H. P. et al. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat. Med. 5, 623\u2013628 (1999).","journal-title":"Nat. Med."},{"key":"503_CR43","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S0925-4773(01)00601-3","volume":"111","author":"C Maes","year":"2002","unstructured":"Maes, C. et al. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Mech. Dev. 111, 61\u201373 (2002).","journal-title":"Mech. Dev."},{"key":"503_CR44","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/emboj.2009.361","volume":"29","author":"C Maes","year":"2010","unstructured":"Maes, C. et al. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J. 29, 424\u2013441 (2010).","journal-title":"EMBO J."},{"key":"503_CR45","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1172\/JCI31581","volume":"117","author":"Y Wang","year":"2007","unstructured":"Wang, Y. et al. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J. Clin. Investig. 117, 1616\u20131626 (2007).","journal-title":"J. Clin. Investig."},{"key":"503_CR46","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1073\/pnas.0708474105","volume":"105","author":"C Wan","year":"2008","unstructured":"Wan, C. et al. Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc. Natl. Acad. Sci. USA 105, 686\u2013691 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"503_CR47","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1002\/jcb.22396","volume":"109","author":"SH Shomento","year":"2010","unstructured":"Shomento, S. H. et al. Hypoxia-inducible factors 1alpha and 2alpha exert both distinct and overlapping functions in long bone development. J. Cell. Biochem. 109, 196\u2013204 (2010).","journal-title":"J. Cell. Biochem."},{"key":"503_CR48","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/nature13145","volume":"507","author":"AP Kusumbe","year":"2014","unstructured":"Kusumbe, A. P., Ramasamy, S. K. & Adams, R. H. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507, 323\u2013328 (2014).","journal-title":"Nature"},{"key":"503_CR49","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1172\/JCI97794","volume":"128","author":"N Dirckx","year":"2018","unstructured":"Dirckx, N. et al. Vhl deletion in osteoblasts boosts cellular glycolysis and improves global glucose metabolism. J. Clin. Investig. 128, 1087\u20131105 (2018).","journal-title":"J. Clin. Investig."},{"key":"503_CR50","doi-asserted-by":"publisher","first-page":"8673","DOI":"10.1073\/pnas.1324290111","volume":"111","author":"JN Regan","year":"2014","unstructured":"Regan, J. N. et al. Up-regulation of glycolytic metabolism is required for HIF1alpha-driven bone formation. Proc. Natl. Acad. Sci. USA 111, 8673\u20138678 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"503_CR51","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1101\/gad.255000.114","volume":"29","author":"C Wu","year":"2015","unstructured":"Wu, C. et al. Oxygen-sensing PHDs regulate bone homeostasis through the modulation of osteoprotegerin. Genes Dev. 29, 817\u2013831 (2015).","journal-title":"Genes Dev."},{"key":"503_CR52","doi-asserted-by":"publisher","first-page":"e112744","DOI":"10.1371\/journal.pone.0112744","volume":"9","author":"J Peng","year":"2014","unstructured":"Peng, J. et al. Dimethyloxalylglycine prevents bone loss in ovariectomized C57BL\/6J mice through enhanced angiogenesis and osteogenesis. PLoS ONE 9, e112744 (2014).","journal-title":"PLoS ONE"},{"key":"503_CR53","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/s13018-022-03162-w","volume":"17","author":"L Li","year":"2022","unstructured":"Li, L., Li, A., Zhu, L., Gan, L. & Zuo, L. Roxadustat promotes osteoblast differentiation and prevents estrogen deficiency-induced bone loss by stabilizing HIF-1alpha and activating the Wnt\/beta-catenin signaling pathway. J. Orthop. Surg. Res. 17, 286 (2022).","journal-title":"J. Orthop. Surg. Res."},{"key":"503_CR54","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1002\/jor.20886","volume":"27","author":"X Shen","year":"2009","unstructured":"Shen, X. et al. Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J. Orthop. Res. 27, 1298\u20131305 (2009).","journal-title":"J. Orthop. Res."},{"key":"503_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116247","volume":"154","author":"A Lang","year":"2022","unstructured":"Lang, A. et al. MIF does only marginally enhance the pro-regenerative capacities of DFO in a mouse-osteotomy-model of compromised bone healing conditions. Bone 154, 116247 (2022).","journal-title":"Bone"},{"key":"503_CR56","doi-asserted-by":"publisher","first-page":"813","DOI":"10.3389\/fnins.2018.00813","volume":"12","author":"JM Gaspar","year":"2018","unstructured":"Gaspar, J. M. & Velloso, L. A. Hypoxia inducible factor as a central regulator of metabolism\u2014implications for the development of obesity. Front. Neurosci. 12, 813 (2018).","journal-title":"Front. Neurosci."},{"key":"503_CR57","doi-asserted-by":"crossref","unstructured":"Valle-Tenney, R., Melis, S. & Maes, C. Hypoxia signaling in bone physiology and energy metabolism. Curr. Opin. Endocr. Metab. Res. 32, 100473 (2023).","DOI":"10.1016\/j.coemr.2023.100473"},{"key":"503_CR58","doi-asserted-by":"publisher","first-page":"3324","DOI":"10.2337\/db14-0472","volume":"63","author":"L Rahtu-Korpela","year":"2014","unstructured":"Rahtu-Korpela, L. et al. HIF prolyl 4-hydroxylase-2 inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction. Diabetes 63, 3324\u20133333 (2014).","journal-title":"Diabetes"},{"key":"503_CR59","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1002\/jbmr.2210","volume":"29","author":"RJ Fajardo","year":"2014","unstructured":"Fajardo, R. J., Karim, L., Calley, V. I. & Bouxsein, M. L. A review of rodent models of type 2 diabetic skeletal fragility. J. Bone Min. Res. 29, 1025\u20131040 (2014).","journal-title":"J. Bone Min. Res."},{"key":"503_CR60","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1007\/s00125-013-2846-8","volume":"56","author":"MK Montgomery","year":"2013","unstructured":"Montgomery, M. K. et al. Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding. Diabetologia 56, 1129\u20131139 (2013).","journal-title":"Diabetologia"},{"key":"503_CR61","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1017\/S0007114514000051","volume":"111","author":"J Gautam","year":"2014","unstructured":"Gautam, J. et al. Micro-architectural changes in cancellous bone differ in female and male C57BL\/6 mice with high-fat diet-induced low bone mineral density. Br. J. Nutr. 111, 1811\u20131821 (2014).","journal-title":"Br. J. Nutr."},{"key":"503_CR62","doi-asserted-by":"publisher","first-page":"e46057","DOI":"10.1371\/journal.pone.0046057","volume":"7","author":"US Pettersson","year":"2012","unstructured":"Pettersson, U. S., Walden, T. B., Carlsson, P. O., Jansson, L. & Phillipson, M. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS ONE 7, e46057 (2012).","journal-title":"PLoS ONE"},{"key":"503_CR63","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3389\/fendo.2016.00102","volume":"7","author":"EL Scheller","year":"2016","unstructured":"Scheller, E. L. et al. Changes in skeletal integrity and marrow adiposity during high-fat diet and after weight loss. Front. Endocrinol. 7, 102 (2016).","journal-title":"Front. Endocrinol."},{"key":"503_CR64","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.cell.2012.01.051","volume":"149","author":"EB Rankin","year":"2012","unstructured":"Rankin, E. B. et al. The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell 149, 63\u201374 (2012).","journal-title":"Cell"},{"key":"503_CR65","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.kisu.2020.12.002","volume":"11","author":"VH Haase","year":"2021","unstructured":"Haase, V. H. Hypoxia-inducible factor-prolyl hydroxylase inhibitors in the treatment of anemia of chronic kidney disease. Kidney Int. Suppl. 11, 8\u201325 (2021).","journal-title":"Kidney Int. Suppl."},{"key":"503_CR66","doi-asserted-by":"publisher","DOI":"10.1038\/srep35517","volume":"6","author":"G Kerckhofs","year":"2016","unstructured":"Kerckhofs, G. et al. Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography. Sci. Rep. 6, 35517 (2016).","journal-title":"Sci. Rep."},{"key":"503_CR67","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/s41584-019-0274-y","volume":"15","author":"A Gruneboom","year":"2019","unstructured":"Gruneboom, A. et al. Next-generation imaging of the skeletal system and its blood supply. Nat. Rev. Rheumatol. 15, 533\u2013549 (2019).","journal-title":"Nat. Rev. Rheumatol."},{"key":"503_CR68","doi-asserted-by":"publisher","first-page":"4123","DOI":"10.1242\/dev.00559","volume":"130","author":"C Colnot","year":"2003","unstructured":"Colnot, C., Thompson, Z., Miclau, T., Werb, Z. & Helms, J. A. Altered fracture repair in the absence of MMP9. Development 130, 4123\u20134133 (2003).","journal-title":"Development"},{"key":"503_CR69","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1172\/JCI80672","volume":"126","author":"C Wang","year":"2016","unstructured":"Wang, C. et al. NOTCH signaling in skeletal progenitors is critical for fracture repair. J. Clin. Investig. 126, 1471\u20131481 (2016).","journal-title":"J. Clin. Investig."},{"key":"503_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22842-5","volume":"12","author":"A Julien","year":"2021","unstructured":"Julien, A. et al. Direct contribution of skeletal muscle mesenchymal progenitors to bone repair. Nat. Commun. 12, 2860 (2021).","journal-title":"Nat. Commun."},{"key":"503_CR71","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1681\/ASN.2019060582","volume":"31","author":"M Sugahara","year":"2020","unstructured":"Sugahara, M. et al. Prolyl hydroxylase domain inhibitor protects against metabolic disorders and associated kidney disease in obese type 2 diabetic mice. J. Am. Soc. Nephrol. 31, 560\u2013577 (2020).","journal-title":"J. Am. Soc. Nephrol."},{"key":"503_CR72","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1038\/s41374-019-0239-4","volume":"99","author":"H Saito","year":"2019","unstructured":"Saito, H. et al. Inhibition of prolyl hydroxylase domain (PHD) by JTZ-951 reduces obesity-related diseases in the liver, white adipose tissue, and kidney in mice with a high-fat diet. Lab Investig. 99, 1217\u20131232 (2019).","journal-title":"Lab Investig."},{"key":"503_CR73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/ham.2018.0076","volume":"20","author":"T Koufakis","year":"2019","unstructured":"Koufakis, T., Karras, S. N., Mustafa, O. G., Zebekakis, P. & Kotsa, K. The effects of high altitude on glucose homeostasis, metabolic control, and other diabetes-related parameters: from animal studies to real life. High. Alt. Med. Biol. 20, 1\u201311 (2019).","journal-title":"High. Alt. Med. Biol."},{"key":"503_CR74","doi-asserted-by":"publisher","first-page":"e15062","DOI":"10.1371\/journal.pone.0015062","volume":"5","author":"CF Bento","year":"2010","unstructured":"Bento, C. F. et al. The chaperone-dependent ubiquitin ligase CHIP targets HIF-1alpha for degradation in the presence of methylglyoxal. PLoS ONE 5, e15062 (2010).","journal-title":"PLoS ONE"},{"key":"503_CR75","doi-asserted-by":"publisher","first-page":"10930","DOI":"10.1074\/jbc.M707451200","volume":"283","author":"DJ Ceradini","year":"2008","unstructured":"Ceradini, D. J. et al. Decreasing intracellular superoxide corrects defective ischemia-induced new vessel formation in diabetic mice. J. Biol. Chem. 283, 10930\u201310938 (2008).","journal-title":"J. Biol. Chem."},{"key":"503_CR76","doi-asserted-by":"publisher","first-page":"13505","DOI":"10.1073\/pnas.0906670106","volume":"106","author":"H Thangarajah","year":"2009","unstructured":"Thangarajah, H. et al. The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proc. Natl. Acad. Sci. USA 106, 13505\u201313510 (2009).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"503_CR77","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.freeradbiomed.2022.03.019","volume":"184","author":"JS Bhatti","year":"2022","unstructured":"Bhatti, J. S. et al. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic. Biol. Med. 184, 114\u2013134 (2022).","journal-title":"Free Radic. Biol. Med."},{"key":"503_CR78","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.7150\/ijms.5630","volume":"10","author":"H Xiao","year":"2013","unstructured":"Xiao, H., Gu, Z., Wang, G. & Zhao, T. The possible mechanisms underlying the impairment of HIF-1alpha pathway signaling in hyperglycemia and the beneficial effects of certain therapies. Int. J. Med. Sci. 10, 1412\u20131421 (2013).","journal-title":"Int. J. Med. Sci."},{"key":"503_CR79","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jacbts.2018.04.005","volume":"3","author":"MS Dodd","year":"2018","unstructured":"Dodd, M. S. et al. Fatty acids prevent hypoxia-inducible factor-1alpha signaling through decreased succinate in diabetes. JACC Basic Transl. Sci. 3, 485\u2013498 (2018).","journal-title":"JACC Basic Transl. Sci."},{"key":"503_CR80","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174583","volume":"912","author":"A Mima","year":"2021","unstructured":"Mima, A. Hypoxia-inducible factor-prolyl hydroxylase inhibitors for renal anemia in chronic kidney disease: advantages and disadvantages. Eur. J. Pharmacol. 912, 174583 (2021).","journal-title":"Eur. J. Pharmacol."},{"key":"503_CR81","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfae051","volume":"17","author":"T Nakanishi","year":"2024","unstructured":"Nakanishi, T. & Kuragano, T. Growing concerns about using hypoxia-inducible factor prolyl hydroxylase inhibitors for the treatment of renal anemia. Clin. Kidney J. 17, sfae051 (2024).","journal-title":"Clin. Kidney J."},{"key":"503_CR82","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1007\/s11914-021-00715-6","volume":"19","author":"V Van Hulten","year":"2021","unstructured":"Van Hulten, V. et al. Fracture patterns in type 1 and type 2 diabetes mellitus: a narrative review of recent literature. Curr. Osteoporos. Rep. 19, 644\u2013655 (2021).","journal-title":"Curr. Osteoporos. Rep."},{"key":"503_CR83","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.cmet.2014.06.003","volume":"20","author":"WP Cawthorn","year":"2014","unstructured":"Cawthorn, W. P. et al. Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab. 20, 368\u2013375 (2014).","journal-title":"Cell Metab."},{"key":"503_CR84","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16878-2","volume":"11","author":"KJ Suchacki","year":"2020","unstructured":"Suchacki, K. J. et al. Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis. Nat. Commun. 11, 3097 (2020).","journal-title":"Nat. Commun."},{"key":"503_CR85","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3389\/fendo.2019.00069","volume":"10","author":"Y Li","year":"2019","unstructured":"Li, Y., Meng, Y. & Yu, X. The unique metabolic characteristics of bone marrow adipose tissue. Front. Endocrinol. 10, 69 (2019).","journal-title":"Front. Endocrinol."},{"key":"503_CR86","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.1210\/clinem\/dgaa216","volume":"105","author":"TT Pham","year":"2020","unstructured":"Pham, T. T. et al. Human bone marrow adipose tissue is a metabolically active and insulin-sensitive distinct fat depot. J. Clin. Endocrinol. Metab. 105, 2300\u20132310 (2020).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"503_CR87","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1007\/s00198-017-4096-y","volume":"28","author":"D Martinez-Laguna","year":"2017","unstructured":"Martinez-Laguna, D. et al. Excess of all-cause mortality after a fracture in type 2 diabetic patients: a population-based cohort study. Osteoporos. Int. 28, 2573\u20132581 (2017).","journal-title":"Osteoporos. Int."},{"key":"503_CR88","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3389\/fendo.2018.00006","volume":"9","author":"C Marin","year":"2018","unstructured":"Marin, C., Luyten, F. P., Van der Schueren, B., Kerckhofs, G. & Vandamme, K. The impact of type 2 diabetes on bone fracture healing. Front. Endocrinol. 9, 6 (2018).","journal-title":"Front. Endocrinol."},{"key":"503_CR89","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.bone.2013.08.003","volume":"57","author":"JA Inzana","year":"2013","unstructured":"Inzana, J. A. et al. Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur. Bone 57, 174\u2013183 (2013).","journal-title":"Bone"},{"key":"503_CR90","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.bonr.2018.04.003","volume":"8","author":"MJ Devlin","year":"2018","unstructured":"Devlin, M. J. et al. Differential effects of high fat diet and diet-induced obesity on skeletal acquisition in female C57BL\/6J vs. FVB\/NJ Mice. Bone Rep. 8, 204\u2013214 (2018).","journal-title":"Bone Rep."},{"key":"503_CR91","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/jcb.22559","volume":"110","author":"DC Genetos","year":"2010","unstructured":"Genetos, D. C. et al. Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblasts. J. Cell. Biochem. 110, 457\u2013467 (2010).","journal-title":"J. Cell. Biochem."},{"key":"503_CR92","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04679-7","volume":"9","author":"S Stegen","year":"2018","unstructured":"Stegen, S. et al. Osteocytic oxygen sensing controls bone mass through epigenetic regulation of sclerostin. Nat. Commun. 9, 2557 (2018).","journal-title":"Nat. Commun."},{"key":"503_CR93","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/ncb2102","volume":"12","author":"J Mazumdar","year":"2010","unstructured":"Mazumdar, J. et al. O2 regulates stem cells through Wnt\/beta-catenin signalling. Nat. Cell Biol. 12, 1007\u20131013 (2010).","journal-title":"Nat. Cell Biol."},{"key":"503_CR94","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s11914-019-00500-6","volume":"17","author":"CE Yellowley","year":"2019","unstructured":"Yellowley, C. E. & Genetos, D. C. Hypoxia Signaling in the Skeleton: Implications for Bone Health. Curr. Osteoporos. Rep. 17, 26\u201335 (2019).","journal-title":"Curr. Osteoporos. Rep."},{"key":"503_CR95","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1172\/JCI35846","volume":"120","author":"K Cheng","year":"2010","unstructured":"Cheng, K. et al. Hypoxia-inducible factor-1alpha regulates beta cell function in mouse and human islets. J. Clin. Investig. 120, 2171\u20132183 (2010).","journal-title":"J. Clin. Investig."},{"key":"503_CR96","doi-asserted-by":"publisher","first-page":"4186","DOI":"10.3390\/ijms25084186","volume":"25","author":"K Yamagata","year":"2024","unstructured":"Yamagata, K., Tsuyama, T. & Sato, Y. Roles of beta-cell hypoxia in the progression of type 2 diabetes. Int. J. Mol. Sci. 25, 4186 (2024).","journal-title":"Int. J. Mol. Sci."},{"key":"503_CR97","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110270","volume":"38","author":"SS Evers","year":"2022","unstructured":"Evers, S. S. et al. Gut HIF2alpha signaling is increased after VSG, and gut activation of HIF2alpha decreases weight, improves glucose, and increases GLP-1 secretion. Cell Rep. 38, 110270 (2022).","journal-title":"Cell Rep."},{"key":"503_CR98","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51718-7","volume":"15","author":"R Wang","year":"2024","unstructured":"Wang, R. et al. Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality. Nat. Commun. 15, 7483 (2024).","journal-title":"Nat. Commun."},{"key":"503_CR99","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s41574-019-0246-y","volume":"15","author":"N Dirckx","year":"2019","unstructured":"Dirckx, N., Moorer, M. C., Clemens, T. L. & Riddle, R. C. The role of osteoblasts in energy homeostasis. Nat. Rev. Endocrinol. 15, 651\u2013665 (2019).","journal-title":"Nat. Rev. Endocrinol."},{"key":"503_CR100","doi-asserted-by":"crossref","unstructured":"Lecka-Czernik, B., Rosen, C. J. & Napoli, N. The role of bone in whole-body energy metabolism. Nat. Rev. Endocrinol. 21, 743\u2013756 (2025).","DOI":"10.1038\/s41574-025-01162-4"},{"key":"503_CR101","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.4","volume":"4","author":"ML Zoch","year":"2016","unstructured":"Zoch, M. L., Abou, D. S., Clemens, T. L., Thorek, D. L. & Riddle, R. C. In vivo radiometric analysis of glucose uptake and distribution in mouse bone. Bone Res. 4, 16004 (2016).","journal-title":"Bone Res."},{"key":"503_CR102","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.devcel.2019.08.013","volume":"51","author":"AM Bohm","year":"2019","unstructured":"Bohm, A. M. et al. Activation of skeletal stem and progenitor cells for bone regeneration is driven by PDGFRbeta signaling. Dev. Cell 51, 236\u2013254.e12 (2019).","journal-title":"Dev. Cell"},{"key":"503_CR103","doi-asserted-by":"crossref","unstructured":"Peredo, N. et al. Visualization and quantification of the stromal-vascular compartment in fetal or adult mouse bones: from sampling to high-resolution 3D image analysis. STAR Protoc. 3, 101222 (2022).","DOI":"10.1016\/j.xpro.2022.101222"},{"key":"503_CR104","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1002\/jbmr.3190","volume":"32","author":"M Dejaeger","year":"2017","unstructured":"Dejaeger, M. et al. Integrin-linked kinase regulates bone formation by controlling cytoskeletal organization and modulating BMP and Wnt signaling in osteoprogenitors. J. Bone Min. Res. 32, 2087\u20132102 (2017).","journal-title":"J. Bone Min. Res."}],"container-title":["Bone Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41413-025-00503-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41413-025-00503-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41413-025-00503-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T05:02:37Z","timestamp":1770786157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41413-025-00503-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":104,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["503"],"URL":"https:\/\/doi.org\/10.1038\/s41413-025-00503-3","relation":{},"ISSN":["2095-6231"],"issn-type":[{"value":"2095-6231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"assertion":[{"value":"20 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21"}}