title: c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines.
abstract: It is widely accepted that the c-Fos gene has a role in proliferation and differentiation of bone cells. ATP-induced c-Fos activation is relevant to bone homeostasis, because nucleotides that are present in the environment of bone cells can contribute to autocrine/paracrine signalling. Gut hormones have previously been shown to have an effect on bone metabolism. In this study, we used the osteoblastic Saos-2 cell line transfected with a c-Fos-driven reporter stimulated with five gut hormones: glucose inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), ghrelin and obestatin, in the presence or absence of ATP. In addition, TE-85 cells were used to determine the time course of c-Fos transcript induction following stimulation with GLP-1, and GLP-2 with or without ATP, using reverse transcription qPCR. The significant results from the experiments are as follows: higher level of c-Fos induction in presence of GIP, obestatin (p = 0.019 and p = 0.011 respectively), and GIP combined with ATP (p < 0.001) using the luciferase assay; GLP-1 and GLP-2 combined with ATP (p = 0.034 and p = 0.002, respectively) and GLP-2 alone (p < 0.001) using qPCR. In conclusion, three of the gut peptides induced c-Fos, providing a potential mechanism underlying the actions of these hormones in bone which can be directed or enhanced by the presence of ATP.
authors.affiliation: Escuela de Medicina, Universidad Anáhuac Mayab, Km 15.5 Carr Merida-Progreso, CP 97310, Mérida, Yucatán, Mexico. elda.pacheco@anahuac.mx.
authors.forename: Elda Leonor
authors.initials: EL
authors.lastname: Pacheco-Pantoja
authors.affiliation: Musculoskeletal Biology Department, Apex Building, 6 West Derby Street, Liverpool, L7 9TX, UK.
authors.forename: Jane P
authors.initials: JP
authors.lastname: Dillon
authors.affiliation: Musculoskeletal Biology Department, Apex Building, 6 West Derby Street, Liverpool, L7 9TX, UK.
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Wilson
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.affiliation: Musculoskeletal Biology Department, Apex Building, 6 West Derby Street, Liverpool, L7 9TX, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Gallagher
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D045744:Cell Line, Tumor; D054439:Ghrelin / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
chemical_list: D054439:Ghrelin; D053767:Glucagon-Like Peptide 2; D016760:Proto-Oncogene Proteins c-fos; D052216:Glucagon-Like Peptide 1; D000255:Adenosine Triphosphate
keywords: ATP; GIP; GLP-1; GLP-2; Osteoblasts; c-Fos