c-Maf and you won’t see fat
Laurie K. McCauley
Laurie K. McCauley
Published September 27, 2010
Citation Information: J Clin Invest. 2010;120(10):3440-3442. https://doi.org/10.1172/JCI44786.
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Commentary

c-Maf and you won’t see fat

Abstract

Osteoporosis is a common, age-related bone disease that results from an imbalance between the processes of bone formation and bone resorption, resulting in reduced bone mass and increased risk of fracture. Mesenchymal stem cells have the capacity to differentiate into osteoblastic and adipogenic lineages; recent research suggests that the switch between these two fates may be key to the decreased bone density that occurs with aging. In this issue, Nishikawa et al. demonstrate that the basic leucine-zipper transcription factor Maf (also known as c-Maf) is central to osteoblast lineage commitment. In addition, they find that increased oxidative stress — as occurs with aging — decreases Maf expression. This work advances understanding of the transcriptional regulation of cell fate decisions and may help direct the development of new therapies to fight age-related bone loss.

Authors

Laurie K. McCauley

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Figure 1

Maf expression determines whether MSCs differentiate toward the adipocyte or osteoblast lineage.

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Maf expression determines whether MSCs differentiate toward the adipocy...
The transcription factor Maf partners with Runx2 to regulate osteoblastic genes, such as osteocalcin (OCN). Maf is downregulated during aging and under the influence of reactive oxygen species (ROS) and thiazolidinediones (TZDs), pharmaceutical drugs for the treatment of diabetes. Downregulation of Maf leads to increased PPARG through the activation of C/EBPδ/α and leads to increased adipogenesis. PPARG itself also downregulates Maf, promulgating a cycle of adipogenesis. Antioxidants promote Maf expression and reverse the adipogenic phenotype, resulting in greater bone formation. Other factors that increase Maf may provide promising therapeutic strategies for the treatment of age-associated bone loss.