title: Oxytocin controls differentiation of human mesenchymal stem cells and reverses osteoporosis.
abstract: 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. Whereas 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 stimulate mesenchymal stem cells osteogenesis at the expense of adipogenesis is of major importance for developing 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 (a stable OT analogue) negatively modulate adipogenesis while promoting osteogenesis in both hMADS cells and human bone marrow mesenchymal stromal cells. 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.
authors.affiliation: ISBDC, Université de Nice Sophia-Antipolis, CNRS, Nice, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Elabd
authors.forename: Armelle
authors.initials: A
authors.lastname: Basillais
authors.forename: Hélène
authors.initials: H
authors.lastname: Beaupied
authors.forename: Véronique
authors.initials: V
authors.lastname: Breuil
authors.forename: Nicole
authors.initials: N
authors.lastname: Wagner
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.forename: Florence
authors.initials: F
authors.lastname: Massiéra
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
authors.forename: Georges
authors.initials: G
authors.lastname: Carle
authors.forename: Liana
authors.initials: L
authors.lastname: Euller-Ziegler
authors.forename: Gérard
authors.initials: G
authors.lastname: Ailhaud
authors.forename: Claude-Laurent
authors.initials: CL
authors.lastname: Benhamou
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
mesh_terms: D050156:Adipogenesis; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D015663:Osteoporosis, Postmenopausal / Q000097:blood; D010052:Ovariectomy; D010121:Oxytocin / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D018045:Receptors, Oxytocin / Q000378:metabolism
chemical_list: D018045:Receptors, Oxytocin; D010121:Oxytocin; C020731:carbetocin