What is it about?

β-catenin is a key downstream effector of the BMP pathway which stimulates bone formation, and has been previously thought to stimulate the formation of osteoblasts (bone forming cells) from bone marrow stem cells. Our study that β-catenin in stem cells actually prevents differentiation , preserves bone marrow stem cells in a multipotential state, and stimulates their proliferation. Further, we show that the effect of β-catenin to promote “stemness” is through activation of EZH2, an enzyme that silences genes through methylation.

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Why is it important?

Understanding molecules key to cell proliferation and differentiation advances our ability to identify novel therapies. β‐catenin and EZH2 are important in regulation gene expression patterns that have to do with cells that form and regenerate tissue. Specifically, these molecules are critical to skeletal health, and may be drug targets for treatment of osteoporosis. Furthermore, EZH2 inhibitors are being actively investigated as potential cancer therapy. By understanding the regulation of EZH2 via β‐catenin in the skeleton, our work has the potential to therapy targets for diverse cancers that involve activation of β--catenin.

Perspectives

I am excited about this work and what it means for the bone metabolism field and for our understanding of the maturation and differentiation of skeletal stem cells. Beyond the bone field and osteoporosis, , I am particularly enthusiastic about the implications of this work for other fields of medicine in which these pathways have been implicated.

Dr Maya Styner
University of North Carolina at Chapel Hill, Department of Medicine, Division of Endocrinology

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This page is a summary of: β‐catenin preserves the stem state of murine bone marrow stromal cells through activation of EZH2, Journal of Bone and Mineral Research, February 2020, Wiley,
DOI: 10.1002/jbmr.3975.
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