Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15

Robert F. Klein, John Allard, Zafrira Avnur, Tania Nikolcheva, David Rotstein, Amy S. Carlos, Marie Shea, Ruth V. Waters, John K. Belknap, Gary Peltz, Eric S. Orwoll

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241 Scopus citations

Abstract

The development of osteoporosis involves the interaction of multiple environmental and genetic factors. Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice. Crossbreeding experiments with Alox15 knockout mice confirmed that 12/15-lipoxygenase plays a role in skeletal development. Pharmacologic inhibitors of this enzyme improved bone density and strength in two rodent models of osteoporosis. These results suggest that drugs targeting the 12/15-lipoxygenase pathway merit investigation as a therapy for osteoporosis.

Original languageEnglish (US)
Pages (from-to)229-232
Number of pages4
JournalScience
Volume303
Issue number5655
DOIs
StatePublished - Jan 9 2004

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    Klein, R. F., Allard, J., Avnur, Z., Nikolcheva, T., Rotstein, D., Carlos, A. S., Shea, M., Waters, R. V., Belknap, J. K., Peltz, G., & Orwoll, E. S. (2004). Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15. Science, 303(5655), 229-232. https://doi.org/10.1126/science.1090985