Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone
العنوان: | Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone |
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المؤلفون: | Sara H Windahl, Gabriel L. Galea, Joanna S. Price, Lance E. Lanyon, Peter J Delisser, Henry Todd, Lee B Meakin |
المصدر: | PLoS ONE PLOS ONE PLoS ONE, Vol 10, Iss 10, p e0140260 (2015) Todd, H, Galea, G L, Meakin, L B, Delisser, P J, Lanyon, L E, Windahl, S H & Price, J S 2015, ' Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone ', PLoS ONE, vol. 10, no. 10, e0140260 . https://doi.org/10.1371/journal.pone.0140260 |
سنة النشر: | 2015 |
مصطلحات موضوعية: | Male, medicine.medical_specialty, Aging, animal structures, medicine.drug_class, Ovariectomy, Osteoporosis, lcsh:Medicine, Estrogen receptor, 030209 endocrinology & metabolism, Biology, Weight-Bearing, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, medicine, Animals, lcsh:Science, 10. No inequality, 030304 developmental biology, Bone mineral, 0303 health sciences, Multidisciplinary, Tibia, lcsh:R, Estrogen Receptor alpha, Estrogens, Bone fracture, medicine.disease, Mice, Inbred C57BL, Wnt Proteins, medicine.anatomical_structure, Endocrinology, Gene Expression Regulation, Estrogen, lcsh:Q, Cortical bone, Female, Bone marrow, Estrogen receptor alpha, Research Article |
الوصف: | Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα) depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse) mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an obligatory contributor to regulation of bone mass per se, it potentially plays a role in influencing pathways associated with regulation of bone mass during ageing and estrogen withdrawal. |
وصف الملف: | application/pdf |
تدمد: | 1932-6203 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de9435ea0c06128b46baad030404c4e7 https://pubmed.ncbi.nlm.nih.gov/26451596 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....de9435ea0c06128b46baad030404c4e7 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 19326203 |
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