Abstract
Chronic administration of glucocorticoids are being linked to an increased risk of osteoporosis. 5-Hydroxymethylfurfural (5-HMF) is a natural compound that possesses various biological activities, including osteogenic regulation. In this research, we sought to investigate the potential of 5-HMF to exert protective effects against glucocorticoid-induced osteoporosis. In cellular investigations, we deployed Western Blot (WB), Real-Time Quantitative real-time PCR (qRT-PCR), Alkaline phosphatase (ALP) and Alizarin S-red (ARS) staining to scrutinize the expression of osteogenic differentiation markers within MC3T3-E1 pre-osteoblasts and BMSCs. We used dexamethasone to establish a mouse model for glucocorticoid-Induced osteoporosis and administered 5-HMF to evaluate its influence on bone density and architecture through the use of micro-CT and histological analysis. In addition, we employed network pharmacology to elucidate the potential pathways and targets of 5-HMF. Finally, we explored the effect of AKT knockout on the treatment of 5-HMF. We found that 5-HMF significantly enhanced VEGFR2 phosphorylation, reestablishing angiogenesis and activating the PI3K/AKT pathway in vitro and in vivo. 5-HMF also inhibited Dexamethasone -induced apoptosis by regulating Bax and Bcl-2 expression. MK2206, an AKT inhibitor, abrogated 5-HMF’s protective properties against GCs. These results indicate that 5-HMF counteracts the negative effects of GCs on osteoblasts and has good bone-promoting differentiation effects.
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Funding
This study was supported by Double-Hundred Talent Personnel Project of Wuxi Health Committee (BJ2023041) and Research Project of the Health Commission of Jiangsu Province (Z2022027).
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Yu Jiang and Fei Fang conceived and designed the study. Siqi Liu wrote the manuscript, translated the manuscript, made manuscript revisions. All authors have read and approved the manuscript.
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Animal procedures followed the regulations of the animal care committee, which were approved by the Institutional Animal Care and Use Committee of Jiangnan University, approval number JN.No 20221120t0180415, and the experiments were performed in accordance with the approved guidelines and regulations. The experiments complied with the ARRIVE guidelines.
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Liu, S., Fang, F. & Jiang, Y. 5-HMF inhibits glucocorticoid-induced osteoporosis through the VEGFR2/PI3K/AKT pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44463-y
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DOI: https://doi.org/10.1038/s41598-026-44463-y
