{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:32:48Z","timestamp":1790487168640,"version":"4.1.0"},"reference-count":29,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5655","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2004,1,9]]},"abstract":"<jats:p>\n            The development of osteoporosis involves the interaction of multiple environmental and genetic factors. Through combined genetic and genomic approaches, we identified the lipoxygenase gene\n            <jats:italic>Alox15<\/jats:italic>\n            as a negative regulator of peak bone mineral density in mice. Crossbreeding experiments with\n            <jats:italic>Alox15<\/jats:italic>\n            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.\n          <\/jats:p>","DOI":"10.1126\/science.1090985","type":"journal-article","created":{"date-parts":[[2004,1,9]],"date-time":"2004-01-09T06:57:46Z","timestamp":1073631466000},"page":"229-232","source":"Crossref","is-referenced-by-count":241,"title":["Regulation of Bone Mass in Mice by the Lipoxygenase Gene\n            <i>Alox15<\/i>"],"prefix":"10.1126","volume":"303","author":[{"given":"Robert F.","family":"Klein","sequence":"first","affiliation":[{"name":"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."},{"name":"Department of Orthopaedics and Rehabilitation, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA."},{"name":"Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA."},{"name":"Veterans Affairs Medical Center, 3710 Southwest U.S. Veterans Hospital Road, Portland, OR 97207, USA."},{"name":"Department of Genetics and Genomics, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Allard","sequence":"additional","affiliation":[{"name":"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."},{"name":"Department of Orthopaedics and Rehabilitation, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA."},{"name":"Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA."},{"name":"Veterans Affairs Medical Center, 3710 Southwest U.S. Veterans Hospital Road, Portland, OR 97207, USA."},{"name":"Department of Genetics and Genomics, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zafrira","family":"Avnur","sequence":"additional","affiliation":[{"name":"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."},{"name":"Department of Orthopaedics and Rehabilitation, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA."},{"name":"Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA."},{"name":"Veterans Affairs Medical Center, 3710 Southwest U.S. Veterans Hospital Road, 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Dis."},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/jnci\/92.14.1136","volume":"92","year":"2000","unstructured":"I. Shureiqiet al., J. Natl. Cancer Inst.92, 1136 (2000).","journal-title":"J. Natl. Cancer Inst."},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000020643","volume":"8","year":"2000","unstructured":"A. Montero, K. F. Badr, Exp. Nephrol.8, 14(2000).","journal-title":"Exp. Nephrol."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1161\/01.ATV.21.4.560","volume":"21","year":"2001","unstructured":"M. Inoueet al., Arterioscler. Thromb. Vasc. Biol.21, 560 (2001).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0022-2275(20)32377-4","volume":"41","year":"2000","unstructured":"J. Fenget al., J. Lipid Res.41, 688 (2000).","journal-title":"J. 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M. Olson, Mamm. Genome10, 327 (1999).","journal-title":"Mamm. Genome"},{"key":"e_1_3_1_30_2","unstructured":"We thank V. K. Chambers D. Dinulescu J. Guo B. Hansen J. Kansagor D. A. Olson B. Orwoll B. Skinner R. J. Turner and K. A. Vartanian for technical assistance. This work was supported by funds from the Northwest Health Foundation Veterans Affairs Medical Research Service and the NIH (AR44659 awarded to R.F.K. and HG02322 awarded to G.P.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1090985","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:31:25Z","timestamp":1704857485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1090985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1,9]]},"references-count":29,"journal-issue":{"issue":"5655","published-print":{"date-parts":[[2004,1,9]]}},"alternative-id":["10.1126\/science.1090985"],"URL":"https:\/\/doi.org\/10.1126\/science.1090985","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1,9]]}}}