title: Glucose-Dependent Insulinotropic Peptide Prevents Serum Deprivation-Induced Apoptosis in Human Bone Marrow-Derived Mesenchymal Stem Cells and Osteoblastic Cells.
abstract: Human bone marrow-derived mesenchymal stem cells (hBMSC) are able to differentiate into cells of connective tissue lineages, including bone and cartilage. They are therefore considered as a promising tool for the treatment of bone degenerative diseases. One of the major issues in regenerative cell therapy is the biosafety of fetal bovine serum used for cell culture. Therefore, the development of a culture medium devoid of serum but preserving hBMSC viability will be of clinical value. The glucose-dependent insulinotropic peptide (GIP) has an anti-apoptotic action in insulin-producing cells. Interestingly, GIP also exerts beneficial effects on bone turnover by acting on osteoblasts and osteoclasts. We therefore evaluated the ability of GIP to prevent cell death in osteoblastic cells cultured in serum-free conditions. In hBMSC and SaOS-2 cells, activation of the GIP receptor increased intracellular cAMP levels. Serum deprivation induced apoptosis in SaOS-2 and hBMSC that was reduced by 30 and 50 %, respectively, in the presence of GIP. The protective effect of GIP involves activation of the adenylate cyclase pathway and inhibition of caspases 3/7 activation. These findings demonstrate that GIP exerts a protective action against apoptosis in hBMSC and suggest a novel approach to preserve viability of hBMSC cultured in the absence of serum.
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.
authors.forename: J L
authors.initials: JL
authors.lastname: Berlier
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Kharroubi
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Dalla Valle
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Rigutto
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Mathieu
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium.|Department of Rheumatology and Physical Medicine, Hôpital Erasme, Université libre de Bruxelles, Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Gangji
authors.affiliation: Laboratory of Bone and Metabolic Biochemistry, Faculty of Medicine, Université libre de Bruxelles, 808 Route de Lennik, 1070, Brussels, Belgium. jrasscha@ulb.ac.be.
authors.forename: J
authors.initials: J
authors.lastname: Rasschaert
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D053179:Caspase 7
keywords: Apoptosis; Glucose-dependent insulinotropic peptide; Human bone marrow-derived mesenchymal stem cells; Serum deprivation; cAMP accumulation