Miranda, CristinaGiner, MercèMontoya, M JoséVázquez, M AngelesMiranda, M JoséPérez-Cano, Ramón2016-09-292016-09-292016-08-31Miranda C, Giner M, Montoya MJ, Vázquez MA, Miranda MJ, Pérez-Cano R. Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression. BMC Musculoskelet Disord. 2016; 17:377http://hdl.handle.net/10668/2434Journal Article;BACKGROUND Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB). METHODS We recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 μg/ml) for 24 h. RESULTS The hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group. CONCLUSIONS Our data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.enRemodelación óseaDiabetes mellitus tipo IIGlucosaGlicosilaciónFracturas de caderaOsteoartritis de la caderaOsteoblastosFracturas osteoporóticasLigando RANKReceptor de productos finales de la glicosilación avanzadaMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Bone RemodelingMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::GlucoseMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Carbohydrate Metabolism::GlycosylationMedical Subject Headings::Diseases::Wounds and Injuries::Fractures, Bone::Hip FracturesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::IncidenceMedical Subject Headings::Diseases::Musculoskeletal Diseases::Joint Diseases::Arthritis::Osteoarthritis::Osteoarthritis, HipMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::OsteoblastsMedical Subject Headings::Diseases::Wounds and Injuries::Fractures, Bone::Osteoporotic FracturesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors::RANK LigandMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Advanced Glycosylation End Product-Specific Receptorresearch article27582133open access10.1186/s12891-016-1228-z1471-2474PMC5007697