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Loss of wnt/β-catenin signaling leads to an osteoblast to adipocyte shift



DOI:10.1038/bonekey.2012.174

The impact of knocking out β-catenin in early osterix-expressing osteoblasts was investigated in transgenic mice. Deletion of β-catenin was achieved by suppressing cre expression in osterix-cre mice by administering doxycycline (Dox) in drinking water to pregnant mice and their young.

At four months Dox treatment was stopped to allow cre expression; two months later, mice showed a great increase in bone marrow adiposity, with marrow fat in the trabecular bone in regions of primary and secondary ossification. This led to an increase in trabecular bone and a decrease in overall bone mass.

When cells obtained from the knockout mice were cultured and assessed, it was clear that bone marrow stem cells were differentiating into adipocytes rather than osteocytes due to reprogramming as a direct result of the loss of wnt signaling. Song et al. then performed an extensive set of experiments in vivo, confirming that β-catenin loss from osteoblast precursors, leading to a shift in cell-fate, was at least partly responsible for the phenotypic effects observed.

Editor's comment: This study demonstrates that loss of wnt/β-catenin signaling causes a cell-fate shift of lineage-committed osterix-expressing early osteoblasts to adipocytes, which is correlated with increased expression of PPARγ and C/EBPα. Thus, the increased bone marrow adiposity resulting from aging, unloading or other causes of bone loss may develop via lineage shift of osteoblasts.


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