Intrafibrillar mineralization deficiency and osteogenesis imperfecta mouse bone fragility.
Intrafibrillar mineralization deficiency and osteogenesis imperfecta mouse bone fragility.
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DOI：
10.1016/j.jmbbm.2021.104377
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发表时间：
2021-05
影响因子：
3.9
通讯作者：
Zeng X
中科院分区：
文献类型：
--
作者：
Maghsoudi-Ganjeh M;Samuel J;Ahsan AS;Wang X;Zeng X
成骨不全（OI）是一种脆性骨疾病，已知会导致严重的骨脆性。然而，其超微结构的起源仍然知之甚少。在这项研究中，我们假设原纤维内矿化不足是氧合指数诱导骨脆性的关键因素。为了验证这一假设，我们探讨了机械和超微结构的变化，在OI骨成骨小鼠（oim）模型。同步加速器X射线散射实验表明，oim骨的原纤维内矿化比野生型骨少得多，从而验证了矿物晶体的损失确实主要发生在oim骨的原纤维内空间。同时发现，野生型骨中矿物晶体优先沿纵轴排列，而非野生型骨中矿物晶体排列更随机。此外，它揭示了矿物质晶体的变形更协调的胶原纤维在野生型比oim骨，这表明在oim骨的两个阶段之间的负荷传递恶化。微柱试验结果显示，基因型组骨压缩功（8.2± 0.9MJ/m3）显著小于野生型组（13.9± 2.7MJ/m3）（p<0.05），而两基因型组骨强度差异无统计学意义（p>0.05）。相反，单轴拉伸试验显示野生型骨的极限强度（50± 4.5MPa）显著大于oim骨的极限强度（38± 5.3MPa）（p<0.05）。此外，纳米划痕测试显示，oim骨的韧性远低于野生型骨的韧性（6.6±2.2 GJ/m3对12.6±1.4 GJ/m3）。最后，使用亚板层骨有限元模型的计算机模拟证实了原纤维内矿化减少与观察到的OI骨力学行为变化之间的联系。总之，这些结果提供了重要的机械见解的根本原因，机械质量差的OI骨，从而铺平了道路，未来治疗这种脆性骨疾病。
Osteogenesis imperfecta (OI), a brittle bone disease, is known to result in severe bone fragility. However, its ultrastructural origins are still poorly understood. In this study, we hypothesized that deficient intrafibrillar mineralization is a key contributor to the OI induced bone brittleness. To test this hypothesis, we explored the mechanical and ultrastructural changes in OI bone using the osteogenesis imperfecta murine (oim) model. Synchrotron X-ray scattering experiments indicated that oim bone had much less intrafibrillar mineralization than wild type bone, thus verifying that the loss of mineral crystals indeed primarily occurred in the intrafibrillar space of oim bone. It was also found that the mineral crystals were organized from preferentially in longitudinal axis in wild type bone to more randomly in oim bone. Moreover, it revealed that the deformation of mineral crystals was more coordinated with collagen fibrils in wild type than in oim bone, suggesting that the load transfer deteriorated between the two phases in oim bone. The micropillar test revealed that the compression work to fracture of oim bone (8.2±0.9 MJ/m3) was significantly smaller (p<0.05) than that of wild type bone (13.9±2.7 MJ/m3), while the bone strength was not statistically different (p>0.05) between the two genotype groups. In contrast, the uniaxial tensile test showed that the ultimate strength of wild type bone (50±4.5 MPa) was significantly greater (p<0.05) than that of oim bone (38±5.3 MPa). Furthermore, the nanoscratch test showed that the toughness of oim bone was much less than that of wild type bone (6.6±2.2 GJ/m3 vs. 12.6±1.4 GJ/m3). Finally, in silico simulations using a finite element model of sub-lamellar bone confirmed the links between the reduced intrafibrillar mineralization and the observed changes in the mechanical behavior of OI bone. Taken together, these results provide important mechanistic insights into the underlying cause of poor mechanical quality of OI bone, thus pave the way toward future treatments of this brittle bone disease.
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影响因子：
2.4
作者：
Gautieri, Alfonso;Vesentini, Simone;Redaelli, Alberto
通讯作者：
Redaelli, Alberto
DOI：
10.1098/rsif.2015.0701
发表时间：
2015-10-06
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Andriotis OG;Chang SW;Vanleene M;Howarth PH;Davies DE;Shefelbine SJ;Buehler MJ;Thurner PJ
通讯作者：
Thurner PJ
影响因子：
15.9
作者：
BONADIO, J;JEPSEN, KJ;GOLDSTEIN, SA
通讯作者：
GOLDSTEIN, SA
影响因子：
15.9
作者：
Fratzl, P;Paris, O;Landis, WJ
通讯作者：
Landis, WJ
影响因子：
6.9
作者：
Forlino, A;Keene, DR;Marini, JC
通讯作者：
Marini, JC