Lrp5 functions in bone to regulate bone mass

Yajun Cui, Paul J. Niziolek, Bryan T. MacDonald, Cassandra R. Zylstra, Natalia Alenina, Daniel R. Robinson, Zhendong Zhong, Susann Matthes, Christina M. Jacobsen, Ronald A. Conlon, Robert Brommage, Qingyun Liu, Faika Mseeh, David R. Powell, Qi M. Yang, Brian Zambrowicz, Han Gerrits, Jan A. Gossen, Xi He, Michael BaderBart O. Williams, Matthew L. Warman, Alexander G. Robling

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Abstract

The human skeleton is affected by mutations in low-density lipoprotein receptor-related protein 5 (LRP5). To understand how LRP5 influences bone properties, we generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high and low bone mass phenotypes in humans. We found that bone properties in these mice were comparable to bone properties in mice with inherited mutations. We also induced an Lrp5 mutation in cells that form the appendicular skeleton but not in cells that form the axial skeleton; we observed that bone properties were altered in the limb but not in the spine. These data indicate that Lrp5 signaling functions locally, and they suggest that increasing LRP5 signaling in mature bone cells may be a strategy for treating human disorders associated with low bone mass, such as osteoporosis.

Original languageEnglish (US)
Pages (from-to)684-691
Number of pages8
JournalNature Medicine
Volume17
Issue number6
DOIs
StatePublished - Jun 1 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cui, Y., Niziolek, P. J., MacDonald, B. T., Zylstra, C. R., Alenina, N., Robinson, D. R., Zhong, Z., Matthes, S., Jacobsen, C. M., Conlon, R. A., Brommage, R., Liu, Q., Mseeh, F., Powell, D. R., Yang, Q. M., Zambrowicz, B., Gerrits, H., Gossen, J. A., He, X., ... Robling, A. G. (2011). Lrp5 functions in bone to regulate bone mass. Nature Medicine, 17(6), 684-691. https://doi.org/10.1038/nm.2388