Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/96946
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DC Field | Value | Language |
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dc.contributor.author | Raghu Nadhanan, R. | - |
dc.contributor.author | Skinner, J. | - |
dc.contributor.author | Chung, R. | - |
dc.contributor.author | Su, Y. | - |
dc.contributor.author | Howe, P. | - |
dc.contributor.author | Xian, C. | - |
dc.contributor.editor | Shi, X. | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | PLoS One, 2013; 8(8):e71592-1-e71592-12 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2440/96946 | - |
dc.description.abstract | Cancer chemotherapy has been shown to induce long-term skeletal side effects such as osteoporosis and fractures; however, there are no preventative treatments. This study investigated the damaging effects of anti-metabolite methotrexate (MTX) subcutaneous injections (0.75 mg/kg BW) for five days and the potential protective benefits of daily oral gavage of fish oil at 0.5 mL/100 g BW (containing 375 mg of n-3 PUFA/100 g BW), genistein (2 mg/100 g BW), or their combination in young adult rats. MTX treatment alone significantly reduced primary spongiosa height and secondary spongiosa trabecular bone volume. Bone marrow stromal cells from the treated rats showed a significant reduction in osteogenic differentiation but an increase in adipogenesis ex vivo. Consistently, stromal cells had significantly higher mRNA levels of adipogenesis-related proliferator activator activated receptor-γ (PPAR-γ) and fatty acid binding protein (FABP4). MTX significantly increased the numbers of bone-resorbing osteoclasts and marrow osteoclast precursor cell pool while significantly enhancing the mRNA expression of receptor activator for nuclear factor kappa B ligand (RANKL), the RANKL/osteoprotegerin (OPG) ratio, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the bone. Supplementary treatment with fish oil and/or genistein significantly preserved trabecular bone volume and osteogenesis but suppressed MTX-induced adipogenesis and increases in osteoclast numbers and pro-osteoclastogenic cytokine expression. Thus, Fish oil and/or genistein supplementation during MTX treatment enabled not only preservation of osteogenic differentiation, osteoblast number and bone volume, but also prevention of MTX treatment-induced increases in bone marrow adiposity, osteoclastogenic cytokine expression and osteoclast formation, and thus bone loss. | - |
dc.description.statementofresponsibility | Rethi Raghu Nadhanan, Jayne Skinner, Rosa Chung, Yu-Wen Su, Peter R. Howe, Cory J. Xian | - |
dc.language.iso | en | - |
dc.publisher | Public Library of Science | - |
dc.rights | © 2013 Raghu Nadhanan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | - |
dc.source.uri | http://dx.doi.org/10.1371/journal.pone.0071592 | - |
dc.subject | Dietary Supplements | - |
dc.title | Supplementation with fish oil and genistein, individually or in combination, protects bone against the adverse effects of methotrexate chemotherapy in rats | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1371/journal.pone.0071592 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Howe, P. [0000-0001-6546-7742] | - |
dc.identifier.orcid | Xian, C. [0000-0002-8467-2845] | - |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_96946.pdf | Published version | 4.55 MB | Adobe PDF | View/Open |
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