Identification of gender-specific candidate genes that influence bone microarchitecture in chromosome 1.
Identification of gender-specific candidate genes that influence bone microarchitecture in chromosome 1.
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DOI：
10.1007/s00223-012-9687-1
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发表时间：
2013-04
影响因子：
4.2
通讯作者：
Edderkaoui B
中科院分区：
文献类型：
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作者：
Mohan S;Hu Y;Edderkaoui B
鉴定峰值骨量性别二态性遗传基础的研究对于提供预防或治疗代谢性骨疾病的新治疗方法显然很重要。我们在这项研究中的目标是确定可能导致体积（v）骨矿物质密度（BMD）差异的骨骼微观结构，并确定调节性别对骨骼影响的新候选基因。因此，我们使用了在 C57BL/6J (B6) 背景下携带来自 CAST/EiJ (CAST) 小鼠的 BMD1-4 基因座的同系小鼠，与年龄和性别匹配的 B6 小鼠相比，雌性而非雄性同系小鼠显示出更高的 vBMD。为了评估两系小鼠之间的 vBMD 差异，我们进行了微型 CT 测量，发现同系小鼠和 B6 小鼠之间的皮质骨体积按组织体积 (BV/TV) 没有差异。然而，与相应的 B6 小鼠相比，雌性而非雄性同源小鼠的小梁 BV/TV 显着更大，这是由于小梁厚度增加但小梁分离并未减少，表明骨形成而非骨吸收是在雌性而非雄性同源小鼠中观察到的小梁骨表型的原因。为了确定性别候选基因，我们确定了 BMD1-4 位点内 B6 和 CAST 之间的多态性，并进行了基因表达谱分析。我们已经确定 ef-hand 钙结合域 (Efcab2)、伴蛋白、连接蛋白分选蛋白 (Cnst) 和早老素 2 (Psen2) 作为潜在候选基因，通过以性别特异性方式影响小梁厚度来调节骨量。
The studies on the identification of the genetic basis for sexual dimorphism in peak bone mass are obviously important toward providing novel therapeutic approaches to prevent or treat metabolic bone diseases. Our goal in this study is to identify the bone microstructure that could lead to differences in volumetric (v) bone mineral density (BMD) and identify new candidate genes that regulate the gender effect on bone. Therefore, we used a congenic line of mice that carry the BMD1-4 locus from CAST/EiJ (CAST) mice in a C57BL/6J (B6) background and show greater vBMD in female but not male congenics compared to age and gender matched B6 mice. To assess the vBMD variations between the two lines of mice, we performed micro-CT measurements and found no difference in cortical bone volume by tissue volume (BV/TV) between congenics and B6 mice. However, trabecular BV/TV was significantly greater in female but not male congenics compared to corresponding B6 mice which was due to increased trabecular thickness but not reduced trabecular separation suggesting that a bone formation but not a bone resorption is responsible for the trabecular bone phenotype observed in the female but not male congenics. To identify the gender candidate genes, we have determined the polymorphisms between B6 and CAST within the BMD1-4 locus and performed gene expression profiling. We have identified ef-hand calcium binding domain (Efcab2), consortin, connexin sorting protein (Cnst) and presenilin 2 (Psen2) as potential candidate genes that regulate bone mass by influencing trabecular thickness in a gender specific manner.