ArticleBrazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica2025
H2S inhibits high glucose-induced osteoblast injury by inhibiting ferroptosis in diabetic osteoporosis in vitro.
Article in Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
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3 authors.
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Abstract
Diabetic osteoporosis (DOP) is a complication of prolonged hyperglycemia. Hydrogen sulfide (H2S) has been identified as a protective factor in bone development. However, the mechanism by which H2S antagonizes the effects of high glucose (HG) on osteoblasts remains unclear. The effects of HG and H2S on osteoblasts were assessed through transcriptomic and metabolomic sequencing to identify key changes in gene expression and metabolism. Reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), alkaline phosphatase (ALP) activity, mineralization, iron ion levels, malondialdehyde (MDA) levels, cell proliferation, and protein expression were evaluated. Transcriptomic analysis revealed significant upregulation of the ferroptosis pathway in HG-treated osteoblasts. Fer-1 and H2S antagonized the HG-induced decrease in osteoblast cell proliferation, increase in ROS production, decrease in MMP, decrease in ALP, decrease in mineralized nodules, and increase in iron ions and MDA. Transcriptome analysis showed Fer-1 was involved in upregulating the synthesis, secretion, and action of parathyroid hormone and estrogen synthesis, while downregulating the mitogen-activated protein kinases (MAPK) pathway. Metabolomic analysis showed H2S restored glutathione metabolism, reducing pyroglutamic acid and L-5-oxoproline levels. Transcriptome sequencing identified downregulated genes (hmox1, ncoa4) and an upregulated gene (slc40a1) related to ferroptosis in the H2S + HG group compared with the HG group. Western blot analysis indicated H2S increased GPX4 and SLC7A11 levels while reducing ACSL4 expression compared with the HG group. Ferroptosis may be involved in the pathogenesis of DOP and H2S can effectively alleviate osteoblast injury by inhibiting ferroptosis in DOP.
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