1. Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression
- Author
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M. José Miranda, Ramón Pérez-Cano, M. José Montoya, C. Miranda, M. Angeles Vázquez, Mercè Giner, [Miranda, Cristina] Virgen Macarena Univ Hosp, Dept Internal Med, Bone Metab Unit, Seville 41009, Spain, [Giner, Merce] Virgen Macarena Univ Hosp, Dept Internal Med, Bone Metab Unit, Seville 41009, Spain, [Jose Miranda, M.] Virgen Macarena Univ Hosp, Dept Internal Med, Bone Metab Unit, Seville 41009, Spain, [Perez-Cano, Ramon] Virgen Macarena Univ Hosp, Dept Internal Med, Bone Metab Unit, Seville 41009, Spain, [Giner, Merce] Univ Seville, Dept Med, E-41009 Seville, Spain, [Jose Montoya, M.] Univ Seville, Dept Med, E-41009 Seville, Spain, [Angeles Vazquez, M.] Univ Seville, Dept Med, E-41009 Seville, Spain, [Perez-Cano, Ramon] Univ Seville, Dept Med, E-41009 Seville, Spain, Research Project of Excellence, Junta de Andalucia (Spain), RETICEF, [Miranda,C, Miranda,MJ, Pérez-Cano,R] Bone Metabolism Unit, Internal Medicine Department, Virgen Macarena University Hospital, Seville, Spain. [Giner,M, Montoya,MJ, Vázquez,MA, Pérez-Cano,R] Medicine Department, University of Seville, Seville, Spain., and Funding was supported by the Research Project of Excellence, Junta de Andalucía (Spain) (CTS-5360/09) and by ISCIII 2013-RED 12–0043 (RETICEF).
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0301 basic medicine ,Glycation End Products, Advanced ,Male ,Diseases::Wounds and Injuries::Fractures, Bone::Hip Fractures [Medical Subject Headings] ,Type-2 diabetes-mellitus ,Osteoporosis ,Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose [Medical Subject Headings] ,Gene Expression ,Core Binding Factor Alpha 1 Subunit ,Apoptosis ,Osteoarthritis, Hip ,Osteoblastos ,Bone remodeling ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,In-vitro ,0302 clinical medicine ,Glycation ,Osteogenic differentiation ,Medicine ,Orthopedics and Sports Medicine ,Fracturas osteoporóticas ,Aged, 80 and over ,biology ,Receptor de productos finales de la glicosilación avanzada ,Diseases::Musculoskeletal Diseases::Joint Diseases::Arthritis::Osteoarthritis::Osteoarthritis, Hip [Medical Subject Headings] ,Diseases::Wounds and Injuries::Fractures, Bone::Osteoporotic Fractures [Medical Subject Headings] ,Rankl ,Osteoblast ,RUNX2 ,medicine.anatomical_structure ,Messenger-rna ,RANKL ,Sp7 Transcription Factor ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Advanced Glycosylation End Product-Specific Receptor [Medical Subject Headings] ,Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings] ,Female ,Bone Remodeling ,Anatomy::Cells::Connective Tissue Cells::Osteoblasts [Medical Subject Headings] ,Research Article ,Receptor ,musculoskeletal diseases ,medicine.medical_specialty ,Fracture risk ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Carbohydrate Metabolism::Glycosylation [Medical Subject Headings] ,Primary Cell Culture ,030209 endocrinology & metabolism ,Bone and Bones ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Tumor Necrosis Factors::RANK Ligand [Medical Subject Headings] ,03 medical and health sciences ,Rheumatology ,Remodelación ósea ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings] ,Internal medicine ,Diabetes mellitus ,Humans ,Bone ,Glicosilación ,Aged ,Osteoblasts ,business.industry ,Hip Fractures ,RANK Ligand ,Fracturas de cadera ,Osteoprotegerin ,Type 2 Diabetes Mellitus ,Ligando RANK ,medicine.disease ,Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Bone Remodeling [Medical Subject Headings] ,030104 developmental biology ,Endocrinology ,Glucose ,Diabetes Mellitus, Type 2 ,Diabetes mellitus tipo II ,Glucosa ,biology.protein ,business ,Biomarkers ,Osteoporotic Fractures ,Osteoartritis de la cadera - Abstract
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.
- Published
- 2016