Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15

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

Research output: Contribution to journalArticle

236 Citations (Scopus)

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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Lipoxygenase
Osteoporosis
Bone and Bones
Bone Density
Genetic Hybridization
Genes
Enzyme Inhibitors
Drug Delivery Systems
Knockout Mice
Rodentia
12-15-lipoxygenase
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

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

Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15. / Klein, Robert; Allard, John; Avnur, Zafrira; Nikolcheva, Tania; Rotstein, David; Carlos, Amy S.; Shea, Marie; Waters, Ruth V.; Belknap, John; Peltz, Gary; Orwoll, Eric.

In: Science, Vol. 303, No. 5655, 09.01.2004, p. 229-232.

Research output: Contribution to journalArticle

Klein, R, Allard, J, Avnur, Z, Nikolcheva, T, Rotstein, D, Carlos, AS, Shea, M, Waters, RV, Belknap, J, Peltz, G & Orwoll, E 2004, 'Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15', Science, vol. 303, no. 5655, pp. 229-232. https://doi.org/10.1126/science.1090985
Klein R, Allard J, Avnur Z, Nikolcheva T, Rotstein D, Carlos AS et al. Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15. Science. 2004 Jan 9;303(5655):229-232. https://doi.org/10.1126/science.1090985
Klein, Robert ; Allard, John ; Avnur, Zafrira ; Nikolcheva, Tania ; Rotstein, David ; Carlos, Amy S. ; Shea, Marie ; Waters, Ruth V. ; Belknap, John ; Peltz, Gary ; Orwoll, Eric. / Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15. In: Science. 2004 ; Vol. 303, No. 5655. pp. 229-232.
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