title: Metformin rescues the MG63 osteoblasts against the effect of high glucose on proliferation.
abstract: AIMS. To study the proliferation of osteoblasts and genes expression under normal glucose, high glucose, and metformin (Met). METHODS. MG63 osteoblast-like cells were cultured in osteogenic medium supplemented with normal glucose (glucose 5.5 mmol/L) or high glucose (glucose 16.7 mmol/L) and metformin + high glucose (Met 300  μmol/L + glucose 16.7 mmol/L). Proliferation was detected with CCK-8 assay at days 1, 3, and 7. Real-time PCR and Western blot were performed to compare the expression of collagen I (Col I), osteocalcin (OCN), osteoprotegerin (OPG), receptor activator for NF- κB ligand (RANKL), and metal matrix proteinases 1 and 2 (MMP1, MMP2). Alkaline phosphatase (ALP) activity was also detected at days 6, 12, and 18. RESULTS. Exposure to high glucose inhibited the proliferation of osteoblasts (P < 0.05), with suppressed OCN and OPG. Meanwhile, Col I, RANKL, MMP1, and MMP2 were unaffected. Metformin attenuated the suppression on proliferation with increased expression of Col I, OCN, and OPG, meanwhile suppressing MMP1 and MMP2. High glucose lowered the intracellular ALP, while metformin raised it. Metformin attenuated the downregulation of ALP completely at day 6, partly at day 12, but not at day 18. CONCLUSIONS. Metformin attenuated the suppression effect of high glucose to the osteoblast proliferation and gene expression, more prominently in earlier stage.
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Endocrinology and Metabolism, Zhangjiagang First People's Hospital, Zhangjiagang, Jiangsu 215600, China.
authors.forename: Xiaojun
authors.identifier: 0000-0002-2230-9389
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China.
authors.forename: Ge
authors.identifier: 0000-0003-2918-0351
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China.
authors.forename: Bimin
authors.initials: B
authors.lastname: Shi
mesh_terms: D000469:Alkaline Phosphatase / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004794:Enzyme Repression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007700:Kinetics; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D015675:Osteocalcin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053244:Osteoprotegerin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D007004:Hypoglycemic Agents; D053244:Osteoprotegerin; D020011:Protective Agents; C506030:TNFRSF11B protein, human; D015675:Osteocalcin; D008687:Metformin; D000469:Alkaline Phosphatase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1