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Translational and Clinical Research
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Interferon Gamma Inhibits Adipogenesis In Vitro and Prevents Marrow Fat Infiltration in Oophorectomized Mice†
Article first published online: 9 APR 2012
DOI: 10.1002/stem.1063
Copyright © 2012 AlphaMed Press
Additional Information
How to Cite
Vidal, C., Bermeo, S., Li, W., Huang, D., Kremer, R. and Duque, G. (2012), Interferon Gamma Inhibits Adipogenesis In Vitro and Prevents Marrow Fat Infiltration in Oophorectomized Mice. STEM CELLS, 30: 1042–1048. doi: 10.1002/stem.1063
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Author contributions: C.V., R.K., and G.D.: concept design, in vivo and in vitro experiments, data collection and analysis, and preparation of the manuscript; S.B., W.L., and D.H.: in vivo and in vitro experiments, data collection and analysis, and preparation of the manuscript.
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Publication History
- Issue published online: 9 APR 2012
- Article first published online: 9 APR 2012
- Accepted manuscript online: 13 FEB 2012 04:47PM EST
- Manuscript Accepted: 26 JAN 2012
- Manuscript Received: 16 NOV 2011
Funded by
- Australian National Health and Medical Research Council. Grant Number: NHMRC 632767
- Nepean Medical Research Foundation
- Canadian Institutes for Health Research. Grant Number: CIHR MOP 10839
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Keywords:
- Adipogenesis;
- Mesenchymal stem cells;
- Interferon gamma;
- Osteoporosis;
- Aging;
- Osteoimmunology
Abstract
Interferon gamma (IFNγ) has been reported to induce osteoblastogenesis from mesenchymal stem cells (MSCs) both in vitro and in vivo. With ageing, adipocytes outnumber osteoblasts within the bone microenvironment leading to a decrease in bone formation. Since both osteoblasts and adipocytes are of mesenchymal origin, we hypothesized that IFNγ treatment might negatively affect adipogenesis while stimulating osteoblastogenesis in human MSC. To test this hypothesis, human MSCs were induced to differentiate into adipocytes in the presence or absence of osteogenic doses of IFNγ (1, 10, and 100 ng/ml). IFNγ-treated MSC showed a decrease in adipocyte differentiation and lipid deposition when compared with vehicle-treated controls. Additionally, adipogenic markers were significantly decreased by IFNγ treatment at the same doses that have been reported to have a strong osteogenic effect in vitro. Furthermore, DNA binding of peroxisome proliferator-activated receptor gamma was significantly lower in IFNγ-treated differentiating MSC. Subsequently, ovariectomized C57BL6 mice were treated with osteogenic doses of IFNγ three times a week for 6 weeks. In distal femur, treated mice showed significantly higher hematopoiesis concomitant with lower levels of fat volume/total volume, adipocyte number, and expression of adipogenic markers when compared with the vehicle-treated mice. Together, these findings demonstrate that, at osteogenic doses, IFNγ also acts as an inhibitor of adipogenesis in vitro and prevents marrow fat infiltration while favors hematopoiesis in ovariectomized mice. STEM CELLS 2012;30:1042–1048