Overexpression of IGF-binding protein 5 alters mineral and matrix properties in mouse femora: An infrared imaging study

Overexpression of IGF-binding protein 5 alters mineral and matrix properties in mouse femora: An infrared imaging study
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DOI:
10.1007/s00223-004-0076-2
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发表时间:
2005-03-01
影响因子:
4.2
通讯作者:
Canalis, E
Canalis, E
中科院分区:
医学3区
文献类型:
--
作者:
Atti, E;Boskey, AL;Canalis, E

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胰岛素样生长因子(IGFs)的合成代谢作用由IGF-binding proteins(IGFBPs)家族调节。在六种已知的IGFBP中,IGFBP-5被认为在骨形成中起作用。为了研究IGFBP-5对骨矿物质和基质性质的影响,通过傅立叶变换红外成像(FTIRI)评价了在骨钙素启动子控制下过表达IGFBP-5的转基因小鼠的股骨。在骨钙素表达最大时(5周)进行分析。监测的光谱参数包括矿物与基质的比率(指示存在的矿物的相对量)、矿物结晶度(矿物晶体大小和完整性的指数)和胶原蛋白成熟度(反映不可还原和可还原的胶原蛋白交联的比率)。为每个股骨选择多个视野,范围从骨骺到骨干。以前,我们发现这些转基因小鼠显示成骨细胞功能下降和骨质减少。在目前的工作中,FTIRI表明,转基因小鼠相比,野生型有不同的模式的骨矿化和基质成熟。具体而言,皮质骨,原发性松质骨和继发性骨化中心的矿物质-基质比和胶原成熟度值较低。尽管趋势一致,但在所有情况下差异均不具有统计学显著性。矿物结晶度在两组之间没有显著差异,这意味着矿物的晶体成熟不受IGFBP-5过表达的影响。这项研究表明,在骨钙素启动子的控制下过表达IGFBP-5的转基因小鼠的股骨在矿物质和基质分布方面有适度的改变,这与IGF在成骨细胞成熟中的作用一致。
The anabolic effects of insulin-like growth factors (IGFs) are modulated by a family of IGF-binding proteins (IGFBPs). Among the six known IGFBPs, IGFBP-5 is considered to play a role in bone formation. To investigate the effects of IGFBP-5 on bone mineral and matrix properties, femurs from transgenic mice overexpressing IGFBP-5 under the control of the osteocalcin promoter were evaluated by Fourier Transform Infrared Imaging (FTIRI). Analyses were done at the time of maximal osteocalcin expression (5 weeks). The spectroscopic parameters monitored were mineral-to-matrix ratio (indicative of the relative amount of mineral present), mineral crystallinity (index of the mineral crystal size and perfection) and collagen maturity (reflecting the ratio of nonreducible and reducible collagen cross-links). Multiple fields were selected for each femur, ranging from epiphysis to diaphysis. Previously, we showed that these transgenic mice display decreased osteoblastic function and osteopenia. In the present work, FTIRI showed that transgenic mice as compared to wild types have a different pattern of bone mineralization and matrix maturation. Specifically, cortical bone, primary spongiosa, and secondary ossification centers had lower values for mineral-to-matrix ratio and collagen maturity. Differences were not statistically significant in all cases although the trends were consistent. The mineral crystallinity did not vary significantly between the two groups, implying that the crystal maturation of mineral was not affected by IGFBP-5 overexpression. This study demonstrates that femurs from transgenic mice over expressing IGFBP-5 under the control of the osteocalcin promoter have modest alterations in mineral and matrix distribution, consistent with a role of IGF in osteoblast maturation.