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Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation

Nishikawa, Keizo, Nakashima, Tomoki, Takeda, Shu, Isogai, Masashi, Hamada, Michito, Kimura, Ayako, Kodama, Tatsuhiko, Yamaguchi, Akira, Owen, Michael John, Takahashi, Satoru and Takayanagi, Hiroshi 2010. Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation. The Journal of Clinical Investigation 120 (10) , pp. 3455-3465. 10.1172/JCI42528

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Abstract

Aging leads to the disruption of the homeostatic balance of multiple biological systems. In bone marrow multipotent mesenchymal cells undergo differentiation into various anchorage-dependent cell types, including osteoblasts and adipocytes. With age as well as with treatment of antidiabetic drugs such as thiazolidinediones, mesenchymal cells favor differentiation into adipocytes, resulting in an increased number of adipocytes and a decreased number of osteoblasts, causing osteoporosis. The mechanism behind this differentiation switch is unknown. Here we show an age-related decrease in the expression of Maf in mouse mesenchymal cells, which regulated mesenchymal cell bifurcation into osteoblasts and adipocytes by cooperating with the osteogenic transcription factor Runx2 and inhibiting the expression of the adipogenic transcription factor Pparg. The crucial role of Maf in both osteogenesis and adipogenesis was underscored by in vivo observations of delayed bone formation in perinatal Maf(-/-) mice and an accelerated formation of fatty marrow associated with bone loss in aged Maf(+/-) mice. This study identifies a transcriptional mechanism for an age-related switch in cell fate determination and may provide a molecular basis for novel therapeutic strategies against age-related bone diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Last Modified: 04 Jun 2017 08:34
URI: http://orca.cf.ac.uk/id/eprint/80555

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