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成骨不全症小鼠模型中成年骨骼结构和性能的性别依赖性。

Gender-dependence of bone structure and properties in adult osteogenesis imperfecta murine model.

机构信息

Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, 650 E. 25th St., Kansas City, MO 64108, USA.

出版信息

Ann Biomed Eng. 2013 Jun;41(6):1139-49. doi: 10.1007/s10439-013-0793-7. Epub 2013 Mar 28.

DOI:10.1007/s10439-013-0793-7
PMID:23536112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3703620/
Abstract

Osteogenesis imperfecta (OI) is a dominant skeletal disorder characterized by bone fragility and deformities. Though the oim mouse model has been the most widely studied of the OI models, it has only recently been suggested to exhibit gender-dependent differences in bone mineralization. To characterize the impact of gender on the morphometry/ultra-structure, mechanical properties, and biochemical composition of oim bone on the congenic C57BL/J6 background, 4-month-old oim/oim, +/oim, and wild-type (wt) female and male tibiae were evaluated using micro-computed tomography, three-point bending, and Raman spectroscopy. Dramatic gender differences were evident in both cortical and trabecular bone morphological and geometric parameters. Male mice had inherently more bone and increased moment of inertia than genotype-matched female counterparts with corresponding increases in bone biomechanical strength. The primary influence of gender was structure/geometry in bone growth and mechanical properties, whereas the mineral/matrix composition and hydroxyproline content of bone were influenced primarily by the oim collagen mutation. This study provides evidence of the importance of gender in the evaluation and interpretation of potential therapeutic strategies when using mouse models of OI.

摘要

成骨不全症(OI)是一种以骨骼脆弱和畸形为特征的显性骨骼疾病。虽然 oim 小鼠模型是 OI 模型中研究最广泛的模型,但最近才有人提出它在骨矿化方面存在性别依赖性差异。为了描述性别对 oim 骨的形态/超微结构、机械性能和生化成分的影响,我们在 C57BL/J6 近交系背景下评估了 4 月龄的 oim/oim、+/oim 和野生型(wt)雌性和雄性胫骨的 micro-computed tomography、三点弯曲和 Raman 光谱。在皮质骨和小梁骨的形态和几何参数方面,均明显存在显著的性别差异。雄性小鼠具有内在更多的骨量和更大的转动惯量,比基因型匹配的雌性对应物增加了相应的骨生物力学强度。性别主要影响骨生长和机械性能的结构/几何形状,而骨的矿物质/基质组成和羟脯氨酸含量主要受 oim 胶原突变的影响。本研究为使用 OI 小鼠模型评估和解释潜在治疗策略时考虑性别的重要性提供了证据。

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本文引用的文献

1
Comparison of bone tissue properties in mouse models with collagenous and non-collagenous genetic mutations using FTIRI.利用傅里叶变换衰减全反射红外光谱法比较具有胶原和非胶原基因突变的小鼠模型的骨组织特性。
Bone. 2012 Nov;51(5):920-8. doi: 10.1016/j.bone.2012.08.110. Epub 2012 Aug 15.
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Recent advances in osteogenesis imperfecta.成骨不全症的最新进展。
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Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice.尽管成骨不全症小鼠的矿化程度高,但超微结构缺陷导致骨基质硬度降低。
Bone. 2012 Jun;50(6):1317-23. doi: 10.1016/j.bone.2012.03.007. Epub 2012 Mar 16.
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Estrogen receptors α and β have different gender-dependent effects on the adaptive responses to load bearing in cancellous and cortical bone.雌激素受体 α 和 β 对松质骨和皮质骨承受负荷的适应性反应具有不同的性别依赖性影响。
Endocrinology. 2012 May;153(5):2254-66. doi: 10.1210/en.2011-1977. Epub 2012 Mar 13.
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Comparable outcomes in fracture reduction and bone properties with RANKL inhibition and alendronate treatment in a mouse model of osteogenesis imperfecta.在成骨不全症的小鼠模型中,RANKL 抑制剂和阿伦膦酸盐治疗在骨折复位和骨特性方面具有可比性。
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The role of GH/IGF-I-mediated mechanisms in sex differences in cortical bone size in mice.生长激素/胰岛素样生长因子-I 介导的机制在小鼠皮质骨大小的性别差异中的作用。
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Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.人胎血干细胞移植可改善成骨不全症小鼠多尺度组织性能
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Dietary fluoride restriction does not alter femoral biomechanical strength in col1a2-deficient (oim) mice with type I collagen glomerulopathy.在患有I型胶原肾小球病的胶原蛋白α2(Col1a2)缺陷(oim)小鼠中,限制饮食中的氟不会改变股骨的生物力学强度。
J Nutr. 2010 Oct;140(10):1752-6. doi: 10.3945/jn.109.120261. Epub 2010 Aug 19.
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Skeletal muscle weakness in osteogenesis imperfecta mice.成骨不全症小鼠的骨骼肌无力。
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