Oxytocin controls differentiation of human mesenchymal stem cells and reverses osteoporosis

被引:158
作者
Elabd, Christian [1 ]
Basillais, Armelle [2 ]
Beaupied, Helene [2 ]
Breuil, Veronique [3 ,4 ,5 ]
Wagner, Nicole [6 ]
Scheideler, Marcel [7 ]
Zaragosi, Laure-Emmanuelle [1 ]
Massiera, Florence [1 ]
Lemichez, Emmanuel [8 ]
Trajanoski, Zlatko [6 ]
Carle, Georges [3 ,4 ]
Euller-Ziegler, Liana [5 ]
Ailhaud, Gerard [1 ]
Benhamou, Claude-Laurent [2 ]
Dani, Christian [1 ]
Amri, Ez-Zoubir [1 ]
机构
[1] Univ Nice Sophia Antipolis, CNRS, ISBDC, F-06100 Nice, France
[2] IPROS Hop Porte Madeleine, INSERM, U658, Orleans, France
[3] Univ Nice Sophia Antipolis, CNRS, GEPITOS, F-06100 Nice, France
[4] Fac Med, IFR50, Nice, France
[5] CHU Archet 1, Serv Rhumatol, Nice, France
[6] Fac Med Nice, INSERM, U907, F-06034 Nice, France
[7] Graz Univ Technol, Inst Genom & Bioinformat, A-8010 Graz, Austria
[8] Fac Med Nice, INSERM, U627, F-06034 Nice, France
关键词
mesenchymal stem cells; osteoblast; adipocyte; differentiation; osteoporosis; oxytocin;
D O I
10.1634/stemcells.2008-0127
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:2399 / 2407
页数:9
相关论文
共 78 条
[1]   Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females [J].
Abdallah, Basem M. ;
Haack-Sorensen, Mandana ;
Fink, Trine ;
Kassem, Moustapha .
BONE, 2006, 39 (01) :181-188
[2]   Effects of basic fibroblast growth factor and a prostaglandin E2 receptor subtype 4 agonist on osteoblastogenesis and adipogenesis in aged ovariectomized rats [J].
Aguirre, J. Ignacio ;
Leal, Martha E. ;
Rivera, Mercedes F. ;
Vanegas, Sally M. ;
Jorgensen, Marda ;
Wronski, Thomas J. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2007, 22 (06) :877-888
[3]  
Ahdjoudj S, 2004, HISTOL HISTOPATHOL, V19, P151, DOI 10.14670/HH-19.151
[4]  
[Anonymous], 1994, World Health Organ Tech Rep Ser, V843, P1
[5]   BINDING AND STRUCTURAL-PROPERTIES OF OXYTOCIN RECEPTORS IN ISOLATED RAT EPIDIDYMAL ADIPOCYTES [J].
BOLAND, D ;
GOREN, HJ .
REGULATORY PEPTIDES, 1987, 18 (01) :7-18
[6]   Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats [J].
Bonnet, N. ;
Laroche, N. ;
Beaupied, H. ;
Vico, L. ;
Dolleans, E. ;
Benhamou, C. L. ;
Courteix, D. .
JOURNAL OF APPLIED PHYSIOLOGY, 2007, 103 (02) :524-533
[7]   Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling [J].
Bonnet, N. ;
Bernard, P. ;
Beaupied, H. ;
Bizot, J. C. ;
Trovero, F. ;
Courteix, D. ;
Benhamou, C. L. .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2007, 221 (01) :111-118
[8]   Human osteoclasts express oxytocin receptor [J].
Colucci, S ;
Colaianni, G ;
Mori, G ;
Grano, M ;
Zallone, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 297 (03) :442-445
[9]   Functional oxytocin receptors discovered in human osteoblasts [J].
Copland, JA ;
Ives, KL ;
Simmons, DJ ;
Soloff, MS .
ENDOCRINOLOGY, 1999, 140 (09) :4371-4374
[10]   Comparison of multi-lineage cells from human adipose tissue and bone marrow [J].
De Ugarte, DA ;
Morizono, K ;
Elbarbary, A ;
Alfonso, Z ;
Zuk, PA ;
Zhu, M ;
Dragoo, JL ;
Ashjian, P ;
Thomas, B ;
Benhaim, P ;
Chen, I ;
Fraser, J ;
Hedrick, MH .
CELLS TISSUES ORGANS, 2003, 174 (03) :101-109