Bone biomechanical properties in LRP5 mutant mice
Bone biomechanical properties in LRP5 mutant mice
复制标题
DOI：
10.1016/j.bone.2004.02.018
复制
发表时间：
2004-07-01
期刊：
影响因子：
4.1
通讯作者：
Recker, RR
中科院分区：
文献类型：
--
作者：
Akhter, MP;Wells, DJ;Recker, RR
导致高骨量(HBM)表型的突变被认为是通过骨骼对机械负荷的适应性反应而起作用的，导致人类和动物的骨骼更致密和更强壮。HBM家族成员的骨表型的特征是形状正常，特别是在承载部位的骨骼非常致密[癌症研究59(1999)1572]。高骨量(HBM)突变被鉴定为编码低密度脂蛋白受体相关蛋白5(LF-P5)基因第171位氨基酸的甘氨酸到缬氨酸的替代[bone Miner]。决议16(4)(2001)758]。因此，研究的重点是LRP5和G171V突变在骨力学传导反应中的作用[J.bone Miner]。第18(2002)960号决议]。表达人类G171V突变的转基因小鼠已被证明具有与受影响个体非常相似的骨骼表型。在这项研究中，我们发现了由LRP5基因G171V突变驱动的皮质骨和松质骨的生物力学特性(结构和表观材料)、骨量/灰分和骨硬度的差异。与人类一样，LRP5 G171V在调节小鼠骨结构表型方面发挥着重要作用。与非转基因产仔鼠(NTG)相比，HBM HET的这些骨骼表型包括更多的结构和表观材料特性。HBM HET组小鼠的体大小和体重与NTG对照组小鼠相近。然而，在HET小鼠中，LRP5 G171V突变导致骨骼具有更大的结构(股骨干、股骨颈、胫骨、椎体)和表观材料(椎体)强度、骨灰重量百分比(尺骨)和胫骨硬度。尽管G171V小鼠的体重与NTG小鼠相似，但G171V小鼠的骨骼更致密和更坚硬，可能代表着对正常机械刺激的骨形成更敏感，导致骨骼对与体重相关的力过度适应。(C)2004 Elsevier Inc.保留所有权利。
The mutation responsible for the high bone mass (HBM) phenotype has been postulated to act through the adaptive response of bone to mechanical load resulting in denser and stronger skeletons in humans and animals. The bone phenotype of members of a HBM family is characterized by normally shaped bones that are exceptionally dense, particularly at load bearing sites [Cancer Res. 59 (1999) 1572]. The high bone mass (HBM) mutation was identified as a glycine to valine substitution at amino acid residue 171 in the gene coding for lowdensity lipoprotein receptor-related protein 5 (LF-P5) [Bone Miner. Res. 16(4) (2001) 758]. Thus, efforts have focused on the examination of the role of LRP5 and the G171V mutation in bone mechanotransduction responses [J. Bone Miner. Res 18 (2002) 960]. Transgenic mice expressing the human G171V mutation have been shown to have skeletal phenotypes remarkably similar to those seen in affected individuals. In this study, we have identified differences in biomechanical (structural and apparent material) properties, bone mass/ash, and bone stiffness of cortical and cancellous bone driven by the G171V mutation in LRP5.As in humans, the LRP5 G171V plays an important role in regulating bone structural phenotypes in mice. These bone phenotypes include greater structural and apparent material properties in HBM HET as compared to non-transgenic littermates (NTG) mice. Body size and weight in HBM HET were similar to that in NTG control mice. However, the LRP5 G171V mutation in HET mice results in a skeleton that has greater structural (femoral shaft, femoral neck, tibiae, vertebral body) and apparent material (vertebral body) strength, percent bone ash weight (ulnae), and tibial stiffness. Despite similar body weight to NTG mice, the denser and stiffer bones in G171V mice may represent greater bone formation sensitivity to normal mechanical stimuli resulting in an overadaptation of skeleton to weight-related forces. (C) 2004 Elsevier Inc. All rights reserved.