title: Regulation of bone mass in mice by the lipoxygenase gene Alox15.
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.
authors.affiliation: 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
authors.forename: Robert F
authors.initials: RF
authors.lastname: Klein
authors.forename: John
authors.initials: J
authors.lastname: Allard
authors.forename: Zafrira
authors.initials: Z
authors.lastname: Avnur
authors.forename: Tania
authors.initials: T
authors.lastname: Nikolcheva
authors.forename: David
authors.initials: D
authors.lastname: Rotstein
authors.forename: Amy S
authors.initials: AS
authors.lastname: Carlos
authors.forename: Marie
authors.initials: M
authors.lastname: Shea
authors.forename: Ruth V
authors.initials: RV
authors.lastname: Waters
authors.forename: John K
authors.initials: JK
authors.lastname: Belknap
authors.forename: Gary
authors.initials: G
authors.lastname: Peltz
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orwoll
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics* / Q000378:metabolism*; D015519:Bone Density / Q000187:drug effects / Q000235:genetics*; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D020869:Gene Expression Profiling; D008040:Genetic Linkage; D007668:Kidney / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis; D010024:Osteoporosis / Q000201:enzymology; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C475064:12-15-lipoxygenase; C106248:6,11-dihydro-5-thia-11-aza-benzo(a)-fluorene; D004791:Enzyme Inhibitors; D005449:Fluorenes; D016859:Lipoxygenase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase