The mechanical phenotype of biglycan-deficient mice is bone- and gender-specific
The mechanical phenotype of biglycan-deficient mice is bone- and gender-specific
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DOI：
10.1016/j.bone.2005.12.081
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发表时间：
2006-07-01
期刊：
影响因子：
4.1
通讯作者：
Kohn, David H.
中科院分区：
文献类型：
--
作者：
Wallace, Joseph M.;Rajachar, Rupak M.;Kohn, David H.
双糖蛋白聚糖（bgn）是一种富含亮氨酸的小分子蛋白聚糖（SLRP），存在于骨骼组织的细胞外基质中。虽然已知bgn参与成骨细胞前体细胞的生长和分化以及胶原纤维形成的调节，但尚不清楚这些功能如何影响骨的几何和机械特性，这些特性是骨结构功能不可或缺的。由于骨结构和功能的遗传控制是局部和性别特异性的，并且由于有证据表明与遗传缺陷相关的性别特异性效应，因此假设编码bgn的基因的工程缺失将导致骨和性别特异性的皮质骨机械表型。在11周龄的C57 BL 6/129小鼠中，检查了两种性别的股骨和胫骨的中段骨干中的皮质骨。通过四点弯曲试验测定bgn缺陷小鼠相对于野生型对照的表型变化，以确定整个骨（结构）和组织水平的机械性能，以及使用组织形态计量学分析骨几何形状和骨形成。在检查的骨骼中，bgn缺乏对男性胫骨的影响最大，其横截面几何特性和骨矿物质密度的增强伴随着组织水平屈服强度和屈服前结构变形和能量耗散的降低。由于屈服前的性质单独受到影响，这意味着基因缺失导致重要的改变，在矿物质和/或基质/矿物质超微结构，并提出了一个新的理解的功能作用，bgn在调节体内骨矿化。(c)2006年爱思唯尔公司All rights reserved.
Biglycan (bgn) is a small leucine-rich proteoglycan (SLRP) enriched in the extracellular matrix of skeletal tissues. While bgn is known to be involved in the growth and differentiation of osteoblast precursor cells and regulation of collagen fibril formation, it is unclear how these functions impact bone's geometric and mechanical properties, properties which are integral to the structural function of bone. Because the genetic control of bone structure and function is both local- and gender-specific and because there is evidence of gender-specific effects associated with genetic deficiencies, it was hypothesized that the engineered deletion of the gene encoding bgn would result in a cortical bone mechanical phenotype that was bone- and gender-specific. In 11-week-old C57BL6/129 mice, the cortical bone in the mid-diaphyses of the femora and tibiae of both genders was examined. Phenotypic changes in bgn-deficient mice relative to wild type controls were assayed by four-point bending tests to determine mechanical properties at the whole bone (structural) and tissue levels, as well as analyses of bone geometry and bone formation using histomorphometry. Of the bones examined, bgn deficiency most strongly affected the male tibiae, where enhanced cross-sectional geometric properties and bone mineral density were accompanied by decreased tissue-level yield strength and pre-yield structural deformation and energy dissipation. Because pre-yield properties alone were impacted, this implies that the gene deletion causes important alterations in mineral and/or the matrix/mineral ultrastructure and suggests a new understanding of the functional role of bgn in regulating bone mineralization in vivo. (c) 2006 Elsevier Inc. All rights reserved.