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骨形态发生蛋白缺乏小鼠(oim小鼠)骨骼力学性能降低的物质基础。

The material basis for reduced mechanical properties in oim mice bones.

作者信息

Camacho N P, Hou L, Toledano T R, Ilg W A, Brayton C F, Raggio C L, Root L, Boskey A L

机构信息

Research Division, The Hospital of Special Surgery, New York, New York 10021, USA.

出版信息

J Bone Miner Res. 1999 Feb;14(2):264-72. doi: 10.1359/jbmr.1999.14.2.264.

Abstract

Osteogenesis imperfecta (OI), a heritable disease caused by molecular defects in type I collagen, is characterized by skeletal deformities and brittle bones. The heterozygous and homozygous oim mice (oim/+ and oim/oim) exhibit mild and severe OI phenotypes, respectively, serving as controlled animal models of this disease. In the current study, bone geometry, mechanics, and material properties of 1-year-old mice were evaluated to determine factors that influence the severity of phenotype in OI. The oim/oim mice exhibited significantly smaller body size, femur length, and moment of area compared with oim/+ and wild-type (+/+) controls. The oim/oim femur mechanical properties of failure torque and stiffness were 40% and 30%, respectively, of the +/+ values, and 53% and 36% of the oim/+ values. Collagen content was reduced by 20% in the oim/oim compared with +/+ bone and tended to be intermediate to these values for the oim/+. Mineral content was not significantly different between the oim/oim and +/+ bones. However, the oim/oim ash content was significantly reduced compared with that of the oim/+. Mineral carbonate content was reduced by 23% in the oim/oim bone compared with controls. Mineral crystallinity was reduced in the oim/oim and oim/+ bone compared with controls. Overall, for the majority of parameters examined (geometrical, mechanical, and material), the oim/+ values were intermediate to those of the oim/oim and +/+, a finding that parallels the phenotypes of the mice. This provides evidence that specific material properties, such as mineral crystallinity and collagen content, are indicative and possibly predictive of bone fragility in this mouse model, and by analogy in human OI.

摘要

成骨不全症(OI)是一种由I型胶原蛋白分子缺陷引起的遗传性疾病,其特征为骨骼畸形和骨骼脆弱。杂合子和纯合子oim小鼠(oim/+和oim/oim)分别表现出轻度和重度的OI表型,可作为该疾病的对照动物模型。在本研究中,对1岁小鼠的骨骼几何形状、力学性能和材料特性进行了评估,以确定影响OI表型严重程度的因素。与oim/+和野生型(+/+)对照相比,oim/oim小鼠的体型、股骨长度和截面惯性矩显著更小。oim/oim股骨的破坏扭矩和刚度力学性能分别为+/+值的40%和30%,以及oim/+值的53%和36%。与+/+骨相比,oim/oim骨中的胶原蛋白含量降低了20%,且趋向于介于oim/+的这些值之间。oim/oim和+/+骨之间的矿物质含量没有显著差异。然而,与oim/+相比,oim/oim骨的灰分含量显著降低。与对照相比,oim/oim骨中的矿物碳酸盐含量降低了23%。与对照相比,oim/oim和oim/+骨中的矿物结晶度降低。总体而言,对于所检查的大多数参数(几何、力学和材料),oim/+的值介于oim/oim和+/+之间,这一发现与小鼠的表型相似。这提供了证据,表明特定的材料特性,如矿物结晶度和胶原蛋白含量,在该小鼠模型中指示并可能预测骨脆性,类推到人类OI也是如此。

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