title: Expression of glucagon-like peptide-1 receptor and glucose‑dependent insulinotropic polypeptide receptor is regulated by the glucose concentration in mouse osteoblastic MC3T3-E1 cells.
abstract: Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP‑1R) are incretin receptors that play important roles in regulating insulin secretion from pancreatic β cells. Incretin receptors are also thought to play a potential role in bone metabolism. Osteoblasts in animals and humans express GIPR; however, the presence of GLP-1R in these cells has not been reported to date. Thus, the aim of this study was to determine whether GLP-1R and GIPR are expressed in osteoblastic cells, and whether their expression levels are regulated by the extracellular glucose concentration. Mouse osteoblastic MC3T3-E1 cells were cultured in medium containing normal (5.6 mM) or high (10, 20 or 30 mM) glucose concentrations, with or without bone morphogenetic protein-2 (BMP-2). RT-PCR, western blot analysis and immunofluorescence were carried out to determine GIPR and GLP-1R mRNA and protein expression levels. Cell proliferation was also assessed. The GLP-1R and GIPR mRNA expression levels were higher in the MC3T3-E1 cells cultured in medium containing high glucose concentrations with BMP-2 compared with the cells cultured in medium containing normal glucose concentrations with or without BMP-2. GLP-1R protein expression increased following culture in high-glucose medium with BMP-2 compared with culture under normal glucose conditions. However, the cellular localization of GLP-1R was not affected by either glucose or BMP-2. In conclusion, our data demonstrate that the expression of GLP-1R and GIPR is regulated by glucose concentrations in MC3T3-E1 cells undergoing differentiation induced by BMP-2. Our results reveal the potential role of incretins in bone metabolism.
authors.affiliation: Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Emina
authors.initials: E
authors.lastname: Aoyama
authors.affiliation: Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Watari
authors.affiliation: Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Katarzyna Anna
authors.initials: KA
authors.lastname: Podyma-Inoue
authors.affiliation: Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yanagishita
authors.affiliation: Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ono
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D005749:Gastric Inhibitory Polypeptide; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000096:biosynthesis* / Q000378:metabolism; D018027:Receptors, Glucagon / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C041086:gastric inhibitory polypeptide receptor; D005947:Glucose