Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone
Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone
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DOI：
10.1016/j.bone.2008.10.051
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发表时间：
2009-03-01
期刊：
影响因子：
4.1
通讯作者：
Herrmann, Wolfgang
中科院分区：
文献类型：
--
作者：
Herrmann, Markus;Tami, Andrea;Herrmann, Wolfgang
背景：近年来，高同型半胱氨酸血症（HHCY）被认为对骨有不良影响。本研究调查了大鼠实验性HHCY是否诱导骨组织中同型半胱氨酸（HCY）的积累，并伴有骨丢失和骨强度降低。材料与方法：用蛋氨酸（Methe）或同型半胱氨酸（Homo）强化饲料诱导健康大鼠HHCY，并与对照组进行比较。高胱氨酸是两个二硫键连接的HCY分子的产物。组织和血浆HCY，S-腺苷高半胱氨酸（SAH）和S-腺苷甲硫氨酸（SAM）的浓度进行了测定。骨进行了评估，生物力学测试，组织形态计量学，亩CT和测量生化骨营业额markets in plasma.Results：甲基和人的动物开发了一个显着的HHCY，伴随着HCY的组织特异性积累（1300至2000;与对照组）。骨组织中65%的HCY与细胞外基质中的胶原结合。甲基化和人属动物的骨和血浆中的SAH（SAM）比率表现出组织特异性增加，表明甲基化能力降低。HCY在骨中的蓄积以松质骨的明显减少为特征（股骨近端：-25至-35%;股骨远端：-56至-58%，胫骨近端：-28至-43%）。因此，骨强度显着降低（-9至-12%hLD.Conclusion：HCY在骨中的组织特异性积累可能是一个有前途的机制，解释HHCY对骨的不良影响。骨细胞甲基化能力降低可能是另一个相关的病理机制。(C)2008年爱思唯尔公司All rights reserved.
Background: Recently, hyperhomocysteinemia (HHCY) has been suggested to have adverse effects on bone. This study investigated if an experimental HHCY in rats induces an accumulation of homocysteine (HCY) in bone tissue that is accompanied by bone loss and reduced bone strength. Material andMethods: HHCY was induced in healthy rats by either a methionine (Meth) or a homocystine (Homo)-enriched diet and compared with controls. Homocystine is the product of two disulfide linked HCY molecules. Tissue and plasma concentrations of HCY, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were measured. Bones were assessed by biomechanical testing, histomorphometry, mu CT and the measurement of biochemical bone turnover markets in plasma.Results: Meth and Homo animals developed a significant HHCY that was accompanied by a tissue specific accumulation of HCY (1300 to 2000; vs. controls). 65% of HCY in bone was bound to collagen of the extracellular matrix. The SAH ( SAM-ratio in bone and plasma of Meth and Homo animals exhibited a tissue specific increase indicating a reduced methylation capacity. Accumulation of HCY in bone was characterized by a distinct reduction of cancellous bone (proximal femur: -25 to -35%; distal femur -56 to -58%, proximal tibia: -28 to -43%). Accordingly, bone strength was significantly reduced (-9 to -12%).Conclusion: A tissue specific accumulation of HCY in bone may be a promising mechanism explaining adverse effects of HHCY on bone. A reduced methylation capacity of bone cells might be another relevant pathomechanism. (C) 2008 Elsevier Inc. All rights reserved.