{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:14:54Z","timestamp":1790018094679,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1141361"],"award-info":[{"award-number":["GNT1141361"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetes is a major risk factor for osteoporosis, which negatively impacts bone health, but the mechanisms underlying the effects of hyperglycemia on bone marrow mesenchymal\/stromal cells (BMSC) are not fully understood. This study investigated how high glucose levels influence BMSC differentiation, proliferation, viability, and metabolism. The results demonstrated that high glucose inhibits osteogenesis in human BMSC, as evidenced by reduced alkaline phosphatase activity, impaired calcium deposition, and downregulation of key osteogenic genes (RUNX2, ALP). Conversely, high glucose conditions promoted adipogenesis, characterized by increased percentage of cells with lipid droplets, and upregulation of adipogenic genes (PPAR\u03b32, CEBP\u03b1, AdipoQ), suggesting a shift towards fat cell differentiation. Furthermore, BMSC cultured in high glucose showed decreased proliferation, elevated DNA damage, increased oxidative stress, enhanced apoptosis and senescence, particularly in later passages, highlighting the negative impact of hyperglycemia on BMSC viability. Metabolomic profiling of osteogenic and adipogenic differentiation in normal and high glucose conditions revealed key metabolic shifts, with nicotinamide adenine dinucleotide (NAD+) and\n                    <jats:sc>l<\/jats:sc>\n                    \u2010glutamate\/\u03b1\u2010ketoglutarate (\u03b1\u2010KG) identified as critical metabolites driving these processes. Supplementation with NAD+ and \u03b1\u2010KG in high glucose conditions significantly enhanced ALP activity. These findings suggest that high glucose promotes adipogenesis at the expense of osteogenesis, exacerbating cellular damage and accelerating aging in BMSC. The identification of NAD+ and \u03b1\u2010KG as key regulators in this process provides new insights into the metabolic mechanisms behind impaired bone health in diabetes and highlights potential therapeutic avenues to counteract these detrimental effects to better manage diabetes\u2010related bone diseases.\n                  <\/jats:p>","DOI":"10.1002\/jcb.70090","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T09:19:02Z","timestamp":1777108742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hyperglycemia Leads to BMSC Impaired Osteogenesis, Enhanced Adipogenesis, and Altered Metabolism"],"prefix":"10.1002","volume":"127","author":[{"given":"Suzanna","family":"Shirazi","sequence":"first","affiliation":[{"name":"Mesenchymal Stem Cell Laboratory, School of Pharmacy and Biomedical Sciences, College of Health Adelaide University  South Australia Australia"},{"name":"Solid Tumour Program, Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9782-5732","authenticated-orcid":false,"given":"Ezaldeen","family":"Esawi","sequence":"additional","affiliation":[{"name":"Solid Tumour Program, Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide South Australia Australia"},{"name":"South Australian ImmunoGENomics Cancer Institute Adelaide University Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyad D.","family":"Nassar","sequence":"additional","affiliation":[{"name":"Solid Tumour Program, Precision Medicine Theme South Australian Health and Medical Research Institute Adelaide South Australia Australia"},{"name":"South Australian ImmunoGENomics Cancer Institute Adelaide University Adelaide South Australia 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