ArticleThe Journal of biological chemistry
1α,25-Dihydroxyvitamin D3 ameliorates diabetes-induced bone loss by attenuating FoxO1-mediated autophagy.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Integrative bioinformatics and machine learning reveal hub genes and immune signatures bridging type 2 diabetes mellitus, fracture susceptibility, and osteoblast differentiation dysfunction.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- New Aspects of the Pathophysiology of Diabetic Bone Fragility - Type 2 Diabetes Mellitus as a Disease of Accelerated Aging.Current osteoporosis reports · 2025Review
- Bone Health in Children and Adolescents with Type 1 Diabetes: Optimizing Bone Accrual and Preventing Fractures.Nutrients · 2025Review
- Role of vitamins in the development and treatment of osteoporosis (Review).International journal of molecular medicine · 2025Review
- Different Forms of Regulated Cell Death in Type-2-Diabetes-Mellitus-Related Osteoporosis: A Focus on Mechanisms and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- The Critical Role of Autophagy in the Pathogenesis of Diabetic Osteoporosis: Mechanisms and Therapeutic Measures.Drug design, development and therapy · 2025Review
- The Role of Autophagy in the Regulation of Bidirectional Relationships in Diabetic Periodontitis.Journal of inflammation research · 2025Review
- Article
- The Synergistic Effect of Zuogui Pill and Eldecalcitol on Improving Bone Mass and Osteogenesis in Type 2 Diabetic Osteoporosis.Medicina (Kaunas, Lithuania) · 2023Article
- mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.International journal of molecular sciences · 2023Review
- Strontium Ranelate Inhibits Osteoclastogenesis through NF-κB-Pathway-Dependent Autophagy.Bioengineering (Basel, Switzerland) · 2023Article
- 1α,25(OH)International journal of molecular sciences · 2023Article
- Autophagy as a potential mechanism underlying the biological effect of 1,25-Dihydroxyvitamin D3 on periodontitis: a narrative review.BMC oral health · 2023Review
- The Potential of Natural Compounds Regulating Autophagy in the Treatment of Osteoporosis.Journal of inflammation research · 2023Review
- Osmanthus Fragrans Loaded NIPAAM Hydrogel Promotes Osteogenic Differentiation of MC3T3-E1.Gels (Basel, Switzerland) · 2022Article
- Influence of type 2 diabetes microangiopathy on bone mineral density and bone metabolism: A meta-analysis.Heliyon · 2022Article
- Melatonin inhibits autophagy in TM3 cells via AKT/FOXO1 pathway.Molecular biology reports · 2022Article
- LncRNA-AK137033 inhibits the osteogenic potential of adipose-derived stem cells in diabetic osteoporosis by regulating Wnt signaling pathway via DNA methylation.Cell proliferation · 2022Article
- The Role of Estrogens and Vitamin D in Cardiomyocyte Protection: A Female Perspective.Biomolecules · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is vital for maintaining cellular homeostasis through removing impaired organelles. It has recently been found to play pivotal roles in diabetes mellitus (DM), which is associated with increased bone fracture risk and loss of bone density. However, the mechanism whereby autophagy modulates DM-induced bone loss is not fully elucidated. Previous work has shown that 1α,25-Dihydroxyvitamin D3 (1,25D) exerts positive effects on autophagy, thus affecting bone metabolism. Here, we investigated whether autophagy was involved in the regulation of diabetic bone metabolism. Using Micro-CT, Elisa, histology, and histomorphometry analysis, we demonstrated that 1,25D rescues glucose metabolism dysfunction and ameliorates bone loss in diabetic mice. In vitro, 1,25D alleviated primary osteoblast dysfunction and intracellular oxidative stress through reducing prolonged high-glucose-mediated excessive autophagy in primary osteoblasts, reflected by decreased protein level of Beclin1 and LC3. Of note, the autophagy activator rapamycin (RAP) ablated the positive effects of 1,25D in diabetic environment, leading to a marked increase in autolysosomes and autophagosomes, examined by mRFP-GFP-LC3 fluorescence double labeling. The excessive autophagy induced by high glucose was deleterious to proliferation and differentiation of primary osteoblasts. Additionally, biochemical studies identified that PI3K/Akt signaling could be activated by 1,25D, resulting in the inhibition of FoxO1. We confirmed that FoxO1 deficiency alleviated high-glucose-induced autophagy and improved biological functions of primary osteoblasts. Together, our results suggest that the PI3K/Akt/FoxO1 signaling pathway is involved in the osteoprotective effect of 1,25D by attenuating autophagy in diabetes, providing a novel insight for the prevention and treatment of diabetes-caused bone loss.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.