Nanoscale morphology of Type I collagen is altered in the Brtl mouse model of Osteogenesis Imperfecta.
Nanoscale morphology of Type I collagen is altered in the Brtl mouse model of Osteogenesis Imperfecta.
复制标题
DOI：
10.1016/j.jsb.2010.08.003
复制
发表时间：
2011-01
影响因子：
3
通讯作者：
Holl, Mark M. Banaszak
中科院分区：
文献类型：
--
作者：
Wallace, Joseph M.;Orr, Bradford G.;Marini, Joan C.;Holl, Mark M. Banaszak
骨具有复杂的等级结构，其已经进化为在体内发挥结构和代谢作用。由于骨结构的复杂性和影响骨超微结构成分的疾病的数量，重要的是开发定量方法来评估骨纳米级性质。常染色体显性遗传性成骨不全主要由编码I型胶原α1或α2链的基因中的甘氨酸取代（80%）和剪接位点突变（20%）引起。使用超过830个胶原突变的基因型-表型相关性揭示了致命突变位于基质中胶原-配体结合的关键区域。然而，这些相关性很少被扩展到骨中的胶原结构。在此，使用基于原子力显微镜的方法对杂合（Brt 1/+）小鼠（α1（I）G349 C）股骨中I型胶原原纤维的D-周期间距进行成像和定量分析，并与野生型（WT）同窝小鼠进行比较。该疾病系统在col 1 α1等位基因中具有明确的变化，导致胶原蛋白结构的充分表征的改变，其与改变的I型胶原纳米级形态直接相关，如通过D-周期间距测量的。在Brt 1/+骨中，与WT相比，D-周期间距显示出平均和沿骨长度的沿着显著更大的变异性，尽管平均间距没有改变。Brt 1/+骨的胶原D-周期间距的群体分布也有显著差异。这些变化可能是由于突变的胶原结构，或Brt 1/+基质中胶原单体的异质性。这些在纳米级水平上的观察提供了对Brt 1/+骨中骨组成、几何形状和机械完整性变化的结构基础的深入了解。进一步的研究是必要的，这些形态观察纳米级的机械完整性。
Bone has a complex hierarchical structure that has evolved to serve structural and metabolic roles in the body. Due to the complexity of bone structure and the number of diseases which affect the ultrastructural constituents of bone, it is important to develop quantitative methods to assess bone nanoscale properties. Autosomal dominant Osteogenesis Imperfecta results predominantly from glycine substitutions (80%) and splice site mutations (20%) in the genes encoding the α1 or α2 chains of Type I collagen. Genotype-phenotype correlations using over 830 collagen mutations have revealed that lethal mutations are located in regions crucial for collagen-ligand binding in the matrix. However, few of these correlations have been extended to collagen structure in bone. Here, an atomic force microscopy-based approach was used to image and quantitatively analyze the D-periodic spacing of Type I collagen fibrils in femora from heterozygous (Brtl/+) mice (α1(I)G349C), compared to wild type (WT) littermates. This disease system has a well-defined change in the col1α1 allele, leading to a well characterized alteration in collagen protein structure, which are directly related to altered Type I collagen nanoscale morphology, as measured by the D-periodic spacing. In Brtl/+ bone, the D-periodic spacing shows significantly greater variability on average and along the length of the bone compared to WT, although the average spacing was unchanged. Brtl/+ bone also had a significant difference in the population distribution of collagen D-period spacings. These changes may be due to the mutant collagen structure, or to the heterogeneity of collagen monomers in the Brtl/+ matrix. These observations at the nanoscale level provide insight into the structural basis for changes present in bone composition, geometry and mechanical integrity in Brtl/+ bones. Further studies are necessary to link these morphological observations to nanoscale mechanical integrity.
登录
查看更多内容
影响因子：
4.1
作者：
Rauch, F;Travers, R;Glorieux, FH
通讯作者：
Glorieux, FH
影响因子：
2.4
作者：
Israelowitz, M;Rizvi, SWH;von Schroeder, HP
通讯作者：
von Schroeder, HP
影响因子：
15.9
作者：
Fratzl, P;Paris, O;Landis, WJ
通讯作者：
Landis, WJ
影响因子：
5.6
作者：
McBride, DJ;Choe, V;Brodsky, B
通讯作者：
Brodsky, B
影响因子：
15.9
作者：
Misof, K;Landis, WJ;Fratzl, P
通讯作者：
Fratzl, P