Regulation of bone mass in mice by the lipoxygenase gene Alox15

被引：215

作者：

Klein, RF

Allard, J

Avnur, Z

Nikolcheva, T

Rotstein, D

Carlos, AS

Shea, M

Waters, RV

Belknap, JK

Peltz, G

Orwoll, ES

机构：

[1] Oregon Hlth & Sci Univ, Sch Med, Dept Med, Bone & Mineral Res Unit, Portland, OR 97239 USA

[2] Oregon Hlth & Sci Univ, Sch Med, Dept Orthopaed & Rehabil, Portland, OR 97239 USA

[3] Oregon Hlth & Sci Univ, Sch Med, Dept Behav Neurosci, Portland, OR 97239 USA

[4] Vet Affairs Med Ctr, Portland, OR 97207 USA

[5] Roche Palo Alto, Dept Genet & Gen, Palo Alto, CA 94303 USA

[6] Roche Palo Alto, Dept Chem, Palo Alto, CA 94303 USA

来源：

SCIENCE | 2004年 / 303卷 / 5655期

关键词：

D O I：

10.1126/science.1090985

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：229 / 232

页数：4

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