ArticlePloS one2022
High glucose-induced inhibition of osteoblast like MC3T3-E1 differentiation promotes mitochondrial perturbations.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Baseline serum metabolites predict fractures in individuals who were Black and had type 2 diabetes.Frontiers in endocrinology · 2026Trial
- Shared mechanisms of musculoskeletal dysfunction in type 2 diabetes mellitus: Insights into future therapeutic directions (Review).International journal of molecular medicine · 2026Review
- 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
- Heterologous Fibrin Biopolymer for Post-Extraction Alveolar Bone Healing in Streptozotocin-Induced Diabetic Rats.Journal of functional biomaterials · 2026Article
- Three-dimensional (3D) culture-primed placental mesenchymal stem cells decrease cellular heterogeneity, significantly enhancing osteogenesis via improving mitochondrial function.Materials today. Bio · 2026Article
- Bone Organoids: A Novel Tool for Modeling and Managing Skeletal Disorders in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Unveiling metabolic pathways in the hyperglycemic bone: bioenergetic and proteomic analysis of the bone tissue exposed to acute and chronic high glucose.Molecular medicine (Cambridge, Mass.) · 2025Article
- Glabridin Alleviates Oxidative Stress-Induced Osteoporosis by Targeting the Akt/NF-ĸB and Akt/GSK-3β Pathways.International journal of molecular sciences · 2025Article
- Skeletal stem and progenitor cells in bone physiology, ageing and disease.Nature reviews. Endocrinology · 2025Review
- From ROS scavenging to boosted osseointegration: cerium-containing mesoporous bioactive glass nanoparticles functionalized implants in diabetes.Journal of nanobiotechnology · 2024Article
- Rapid correction of chronic hyperglycemia and bone remodeling, warning against overdoing.World journal of diabetes · 2024Review
- Nutrition and Bone Marrow Adiposity in Relation to Bone Health.Physiological research · 2024Review
- A Review of Animal Models for Studying Bone Health in Type-2 Diabetes Mellitus (T2DM) and Obesity.International journal of molecular sciences · 2024Review
- Thioredoxin Interacting Protein Expressed in Osteoblasts Mediates the Anti-Proliferative Effects of High Glucose and Modulates the Expression of Osteocalcin.Journal of bone metabolism · 2024Article
- Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro.Biology open · 2024Article
- Mitochondrial Dysfunction in Periodontitis and Associated Systemic Diseases: Implications for Pathomechanisms and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Healthy and diabetic primary human osteoblasts exhibit varying phenotypic profiles in high and low glucose environments on 3D-printed titanium surfaces.Frontiers in endocrinology · 2024Article
- The Synergistic Effect of Zuogui Pill and Eldecalcitol on Improving Bone Mass and Osteogenesis in Type 2 Diabetic Osteoporosis.Medicina (Kaunas, Lithuania) · 2023Article
- Bone mineralisation and glucose metabolism.Current opinion in endocrine and metabolic research · 2023Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Diabetes mellitus is a metabolic disorder that causes health concerns worldwide. Patients with diabetes exhibit multisystemic symptoms, including loss of bone quality over time. The progressive deterioration of bone promotes failure to withstand damage and increases the risk of fractures. Much of the molecular and metabolic mechanism(s) in diabetic bone remains unclear. In vitro studies suggest that hyperglycemia inhibits mineralization, affecting bone formation and function. In this study, inhibition of osteoblast differentiation was induced using hyperglycemia to assess whether high glucose promotes mitochondrial impairment along with altered bone matrix formation. It was hypothesized that bone energy metabolism would be altered in these cells as calcium deposition, a key phase for bone function, is suppressed. Early passages of osteoblast like MC3T3-E1 cells were differentiated under normal and high glucose conditions. To investigate osteoblast differentiation, we quantified calcium accumulation by alizarin red staining and analyzed immunoblots of key proteins. To assess mitochondrial function, we quantified mitochondrial DNA (mtDNA), detected expression and function of key proteins from the Tricarboxylic (TCA) cycle, measured mitochondrial respiration, and fuel oxidation of alternative nutrients. Results confirmed previous work showing that mineralization was inhibited and AKT expression was reduced in high glucose-treated bone cells. Unexpectedly, high glucose-treated osteoblast cells utilize both mitochondrial respiration and glycolysis to maintain energy demands with partial help of fatty acid for reliance of baseline bioenergetics. These metabolic shifts suggest that hyperglycemia maintain bone metabolic needs in an early differentiated state concurrent to the inhibition in bone matrix formation.
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Registered trials
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