Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15

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Science  09 Jan 2004:
Vol. 303, Issue 5655, pp. 229-232
DOI: 10.1126/science.1090985

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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.

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