The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Increased Lipid Oxidation Causes Oxidative Stress, Increased Peroxisome Proliferator-activated Receptor-γ Expression, and Diminished Pro-osteogenic Wnt Signaling in the Skeleton
Open accessAbstract
Loss of bone mass with advancing age in mice is because of decreased osteoblast number and is associated with increased oxidative stress and decreased canonical Wnt signaling. However, the underlying mechanisms are poorly understood. We report an age-related increase in the lipid oxidation product 4-hydroxynonenal (4-HNE) as well as increased expression of lipoxygenase and peroxisome proliferator-activated receptor-gamma (PPARgamma) in the murine skeleton. These changes together with decreased Wnt signaling are reproduced in 4-month-old mice bearing a high expressing allele of the lipoxygenase Alox15. The addition of 4-HNE to cultured osteoblastic cells increases oxidative stress, which in turn diverts beta-catenin from T-cell-specific transcription factors to Forkhead box O (FoxO) transcription factors, thereby attenuating the suppressive effect of beta-catenin on PPARgamma gene expression. Oxidized lipids, acting as ligands of PPARgamma, promote binding of PPARgamma2 to beta-catenin and reduce the levels of the latter, and they attenuate Wnt3a-stimulated proliferation and osteoblast differentiation. Furthermore, oxidized lipids and 4-HNE stimulate apoptosis of osteoblastic cells. In view of the role of oxidized lipids in atherogenesis, the adverse effects of lipoxygenase-mediated lipid oxidation on the differentiation and survival of osteoblasts may provide a mechanistic explanation for the link between atherosclerosis and osteoporosis.
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Cites
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p53 mutant mice that display early ageing-associated phenotypes
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Cited by
Manolagas, S. C. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0024 · Cited by 1,200
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Chen, Q., Shou, P., Zheng, C., Jiang, M., Cao, G., Yang, Q., Cao, J., Xie, N., Velletri, T., Zhang, X., et al. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.168 · Cited by 1,156
Estrogens and androgens in skeletal physiology and pathophysiology
Almeida, M., Laurent, M. R., Dubois, V., Claessens, F., O'Brien, C. A., Bouillon, R., Vanderschueren, D., & Manolagas, S. C. (2017) · Physiological Reviews · doi:10.1152/physrev.00033.2015 · Cited by 860
Self-citationManolagas, S. C., & Parfitt, A. M. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2010.01.010 · Cited by 404
Self-citationThe Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans
Jilka, R. L. (2013) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glt046 · Cited by 329
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Metadata
- Authors
- Almeida, M., Ambrogini, E., Han, L., Manolagas, S. C., & Jilka, R. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 284
- Issue
- 40
- Pages
- 27438-27448
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2024130717
- Cited by
- 275
- References
- 78
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Increased Lipid Oxidation Causes Oxidative Stress, Increased Peroxisome Proliferator-activated Receptor-γ Expression, and Diminished Pro-osteogenic Wnt Signaling in the Skeleton. https://app.cochat.ai/papers/10.1074/jbc.m109.023572
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- Almeida, M., Ambrogini, E., Han, L., Manolagas, S. C., & Jilka, R. L. (2009). Increased Lipid Oxidation Causes Oxidative Stress, Increased Peroxisome Proliferator-activated Receptor-γ Expression, and Diminished Pro-osteogenic Wnt Signaling in the Skeleton. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.023572
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