Genetic variations that regulate bone morphology in the male mouse skeleton do not define its susceptibility to mechanical unloading

Genetic variations that regulate bone morphology in the male mouse skeleton do not define its susceptibility to mechanical unloading
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DOI:
10.1016/j.bone.2004.08.010
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发表时间:
2004-12-01
期刊:
影响因子:
4.1
通讯作者:
Judex, S
Judex, S
中科院分区:
医学2区
文献类型:
--
作者:
Squire, M;Donahue, LR;Judex, S

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遗传学可以显著地影响骨形态,并且可以定义骨骼对机械卸载的响应。最近的数据表明,废用产生不同的位点特异性反应的骨骼遗传不同的成年雌性C3 H/HeJ(C3 H)和BALB/ cByJ(BALB)小鼠;而废用BALB小鼠有显着较少的骨比年龄匹配的对照组在远端和骨干股骨,负重的去除有一个小得多的影响C3 H。使用来自这两个近交系的成年雄性小鼠,检验了遗传变异和解剖位置之间的相互作用定义骨形态及其对卸载的敏感性的假设。四个月大的雄性BALB和C3 H小鼠进行21天的后肢卸载或作为对照。通过显微计算机断层扫描分析股骨远端和骨干内的多个皮质和骨小梁区域。C3 H对照组的骨干和干骺端皮质骨面积(45%和32%)和干骺端松质骨体积分数(67%)显著高于BALB对照组,但两种品系的骺端松质骨体积分数相似。尽管骨形态存在这些实质性的、位点特异性的差异,但废用在这两种品系中诱导了相似的骨形态变化。与对照组相比,废用BALB和C3 H的干骺端(17%和19%)和骨骺(10%和13%)骨小梁显著减少,而骨干和干骺端皮质骨几何形状不受影响。这些数据表明,两种菌株之间的骨小梁和皮质骨形态的空间不均匀差异引起的遗传变异对特定部位卸载的敏感性影响不大。与来自雌性BALB和C3 H小鼠的先前数据的跨性别比较进一步表明了强相互作用,通过该相互作用,性别、基因型和解剖位置定义了骨骼对去除负重的反应。(C)2004年爱思唯尔公司All rights reserved.
Genetics can substantially influence bone morphology and may define the skeleton's response to mechanical unloading. Recent data indicated that disuse produces different site-specific responses in the skeleton of genetically distinct adult female C3H/HeJ (C3H) and BALB/ cByJ (BALB) mice; while disuse BALB mice had significantly less bone than age-matched controls in the distal and diaphyseal femur, the removal of weight bearing had a much smaller influence in C3H. Using adult male mice from these two inbred strains, the hypothesis was tested that interactions between genetic variations and anatomic location define bone morphology and its susceptibility to unloading. Four-month-old male BALB and C3H mice were either subjected to 21 days of hindlimb unloading or served as controls. Multiple cortical and trabecular regions within the distal and diaphyseal femur were analyzed by micro-computed tomography. C3H controls had significantly greater diaphyseal and metaphyseal cortical bone area (45% and 32%) and greater metaphyseal trabecular bone volume fraction (67%) than BALB controls, but epiphyseal trabecular bone volume fraction was similar between the two strains. Despite these substantial, site-specific differences in bone morphology, disuse induced similar changes in bone morphology in these two strains. Compared to controls, disuse BALB and C3H had significantly less metaphyseal (17% and 19%) and epiphyseal (10% and 13%) trabecular bone, while diaphyseal and metaphyseal cortical bone geometry was unaffected. These data indicate that the genetic variations that caused spatially nonuniform differences in trabecular and cortical bone morphology between the two strains had little influence on the susceptibility of a specific site to unloading. Cross-gender comparisons with previous data from female BALB and C3H mice further suggest strong interactions by which gender, genotype, and anatomical location define the response of the skeleton to the removal of weight bearing. (C) 2004 Elsevier Inc. All rights reserved.