Oxytocin Controls Differentiation of Human Mesenchymal Stem Cells and Reverses Osteoporosis

Autor: Ez-Zoubir Amri, Emmanuel Lemichez, Claude Laurent Benhamou, Liana Euller-Ziegler, Georges F. Carle, Armelle Basillais, Véronique Breuil, Laure-Emmanuelle Zaragosi, Christian Elabd, Zlatko Trajanoski, Florence Massiera, H. Beaupied, Marcel Scheideler, Christian Dani, Nicole Wagner, Gérard Ailhaud
Přispěvatelé: Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Biomécanique et génie biomédical (BIM), Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Génétique, physiopathologie et ingénierie du tissu osseux (GéPITOS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Toxines bactériennes dans la relation hôtes-pathogènes, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Génétique et signalisation moléculaire (GSM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Caractérisation du tissu osseux par imagerie : techniques et applications, Université d'Orléans (UO)-Centre Hospitalier Régional d'Orléans (CHRO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléan (CHRO), Institut de Prévention et de Recherches sur l'ostéoporose, Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions plantes-microorganismes et santé végétale (IPMSV), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Dysfonctions métaboliques et diabètes: Mécanismes et approches thérapeutiques, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Genomics and Bioinformatics, Graz, Karl-Franzens-Universität [Graz, Autriche], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Centre Hospitalier Régional d'Orléans (CHR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Recherche Agronomique (INRA)
Rok vydání: 2008
Předmět:
Male
medicine.medical_specialty
Ovariectomy
Osteoporosis
Osteoclasts
Bone Marrow Cells
030209 endocrinology & metabolism
Biology
Oxytocin
Bone resorption
Bone remodeling
Mice
03 medical and health sciences
0302 clinical medicine
Osteogenesis
Internal medicine
medicine
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
[SDV.BDD]Life Sciences [q-bio]/Development Biology
Cells
Cultured
Osteoporosis
Postmenopausal
Aged
030304 developmental biology
Aged
80 and over
0303 health sciences
Adipogenesis
Osteoblasts
Mesenchymal stem cell
Mesenchymal Stem Cells
Osteoblast
Cell Biology
Middle Aged
medicine.disease
Rats
3. Good health
medicine.anatomical_structure
Endocrinology
Receptors
Oxytocin
Child
Preschool
Ovariectomized rat
Molecular Medicine
Female
Bone marrow
Developmental Biology
Zdroj: Stem Cells / Stem Cells (Miamisburg)
Stem Cells / Stem Cells (Miamisburg), Alphamed Press, 2008, 26 (9), epub ahead of print. ⟨10.1634/stemcells.2008-0127⟩
Stem Cells / Stem Cells (Miamisburg), 2008, 26 (9), epub ahead of print. ⟨10.1634/stemcells.2008-0127⟩
Stem Cells / Stem Cells (Miamisburg), Alphamed Press, 2008, 26 (9), pp.2399-407. ⟨10.1634/stemcells.2008-0127⟩
Stem Cells / Stem Cells (Miamisburg), Alphamed Press, 2008, epub ahead of print. ⟨10.1634/stemcells.2008-0127⟩
ISSN: 1549-4918
1066-5099
DOI: 10.1634/stemcells.2008-0127
Popis: Osteoporosis constitutes a major worldwide public health burden characterized by enhanced skeletal fragility. Bone metabolism is the combination of bone resorption by osteoclasts and bone formation by osteoblasts. While increase in bone resorption is considered as the main contributor of bone loss that may lead to osteoporosis, this loss is accompanied by increased bone marrow adiposity. Osteoblasts and adipocytes share the same precursor cell and an inverse relationship exists between the two lineages. Therefore, identifying signaling pathways that stimulates mesenchymal stem cells osteogenesis at the expense of adipogenesis is of major importance in order to develop new therapeutic treatments. For this purpose, we identified by transcriptomic analysis the oxytocin receptor pathway as a potential regulator of the osteoblast/adipocyte balance of human multipotent adipose-derived stem (hMADS) cells. Both oxytocin (OT) and carbetocin (Cb, a stable OT analogue) negatively modulate adipogenesis while promoting osteogenesis in both hMADS cells and human bone marrow mesenchymal stromal cells (hBMSC). Consistent with these observations ovariectomized (OVX) mice and rats, which become osteoporotic and exhibit disequilibrium of this balance, have significant decreased OT levels compared to sham-operated controls. Subcutaneous OT injection reverses bone loss in OVX mice and reduces marrow adiposity. Clinically, plasma OT levels are significantly lower in postmenopausal women developing osteoporosis than in their healthy counterparts. Taken together, these results suggest that plasma OT levels represent a novel diagnostic marker for osteoporosis and that OT administration holds promise as a potential therapy for this disease. ______________________________________________________________________________ Author contributions: C.E.: carried out most of the experiments, data analysis and interpretation, collection and assembly of data; A.B., H.B. and C.B.: analysis of bone micro-architecture and biomechanical parameters of mice, manuscript writing; L.Z., M.S. and Z.T.: microarray analysis, data analysis and interpretation; F.M.: contribution to the mice study, data analysis and interpretation; V.B., G.F.C. and L.E.: provision of patients, data analysis and interpretation; N.W.: histological analysis of mice tissues, data analysis and interpretation; E.L.: provision of study material, data analysis and interpretation; C.D.: data analysis and interpretation, manuscript writing; G.A.: conception and design, data analysis and interpretation, manuscript writing; E.A.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing.
Databáze: OpenAIRE
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