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Disrupting PPARγ: how this affects bone remodeling


Cao et al. have performed the first relevant gene knockout studies in mice to find out more about the mechanism by which peroxisome proliferator-activated receptor gamma (PPARγ) regulates adipogenesis in bone.

DXA scanning showed that mice lacking PPARγ in cells that express a 3.6 kb type I collagen promoter fragment (PPARfl/fl:Col3.6-Cre) had very similar bone mineral density and bone mineral content as normal controls at the age of 8 weeks. By the time the mice were three months old, a significant but moderate increase in BMD and BMC was detected, but only at the lumbar spine and in male knockout mice only.

Analysis of primary bone cultures and bone marrow mesenchymal stem cells from the knockout mice revealed a complete abolition of adipogenesis and a significant increase in osteoblastogenesis. PPARγ knockout mice also had significantly higher numbers of osteoblasts but the differentiation and production of osteoclasts was apparently unaffected.

Editor's comment: Conditional deletion of the adipogenic transcription factor PPARγ in pre-osteoblasts confirms and extends the evidence that this transcription factor is a negative regulator of osteoblasts development and bone mass. Many other interesting studies on diet, fat and bone can be found in this special issue of Molecular Cell Endocrinology.

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