Publication Date:
2004-01-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, Robert F -- Allard, John -- Avnur, Zafrira -- Nikolcheva, Tania -- Rotstein, David -- Carlos, Amy S -- Shea, Marie -- Waters, Ruth V -- Belknap, John K -- Peltz, Gary -- Orwoll, Eric S -- AR44659/AR/NIAMS NIH HHS/ -- HG02322/HG/NHGRI NIH HHS/ -- R01 AR044659/AR/NIAMS NIH HHS/ -- R01 AR044659-08/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 9;303(5655):229-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bone and Mineral Research Unit, Department of Medicine, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA. kleinro@ohsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14716014" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Arachidonate 12-Lipoxygenase/*genetics/*metabolism
;
Arachidonate 15-Lipoxygenase/*genetics/*metabolism
;
Bone Density/drug effects/*genetics
;
Bone Marrow Cells/metabolism
;
Cell Differentiation
;
Cells, Cultured
;
Crosses, Genetic
;
Enzyme Inhibitors/pharmacology
;
Female
;
Fluorenes/pharmacology
;
Gene Expression Profiling
;
Genetic Linkage
;
Kidney/metabolism
;
Lipoxygenase Inhibitors
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Inbred Strains
;
Mice, Knockout
;
Mice, Transgenic
;
Oligonucleotide Array Sequence Analysis
;
Osteoblasts/cytology/metabolism/physiology
;
Osteogenesis
;
Osteoporosis/enzymology
;
Polymorphism, Genetic
;
Quantitative Trait Loci
;
Rats
;
Receptors, Cytoplasmic and Nuclear/metabolism
;
Stromal Cells/metabolism
;
Transcription Factors/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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