PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures
PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures
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DOI：
10.1016/j.bone.2011.01.010
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发表时间：
2011-05-01
期刊：
影响因子：
4.1
通讯作者：
Farquharson, Colin
中科院分区：
文献类型：
--
作者：
Huesa, Carmen;Yadav, Manisha C.;Farquharson, Colin
磷酸酶对于骨骼内细胞外基质的矿化至关重要。然而，它们的确切身份和功能仍不清楚。PHOSPHO1是一种磷酸乙醇胺/磷酸胆碱磷酸酶，参与骨矿化所需无机磷酸盐的生成。它在骨和软骨的矿化部位高度表达。Phospho1（-/-）小鼠的骨骼矿化不足，弯曲，出生时出现自发性青枝骨折。在这项研究中，我们表明PHOSPHO1对于能够承受常规负荷的具有机械性能的矿化至关重要。Phospho1（-/-）小鼠的长骨在三点弯曲过程中未断裂，但发生了塑性变形。通过动态加载纳米压痕技术，Phospho1（-/-）胫骨的弹性模量和硬度显著低于野生型胫骨。拉曼显微镜显示Phospho1（-/-）胫骨的矿物质与基质的比率显著降低，碳酸盐替代也减少。二羟赖氨酰正亮氨酸/羟赖氨酰正亮氨酸和吡啶啉/脱氧吡啶啉胶原蛋白交联比率的改变表明赖氨酰羟化酶 - 1活性和/或骨矿化状态可能发生变化。1型胶原蛋白的N - 末端前肽和C - 末端肽这两种骨形成和吸收标志物在Phospho1（-/-）小鼠中均升高，我们将此与骨折修复过程中骨重塑增加或试图重塑能够承受生理负荷的具有机械性能的骨骼相关联。总之，这些数据表明Phospho1（-/-）小鼠的骨骼矿化不足，因此更软且更具柔韧性。无法承受生理负荷可能解释了所观察到的变形。我们假设这种表型是由于矿化过程中可用于形成羟基磷灰石的无机磷酸盐减少，导致骨骼矿化不足但仍处于活跃状态。（C）2011爱思唯尔公司。保留所有权利。
Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1(-/-) mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this study we show that PHOSPHO1 is essential for mechanically competent mineralization that is able to withstand habitual load. Long bones from Phospho1(-/-) mice did not fracture during 3-point bending but deformed plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1(-/-) tibiae were significantly lower than wild-type tibia. Raman microscopy revealed significantly lower mineral:matrix ratios and lower carbonate substitutions in Phospho1(-/-) tibia. The altered dihydroxylysinonorleucine/hydroxylysinonorleucine and pyridinoline/deoxypyridinoline collagen crosslink ratios indicated possible changes in lysyl hydroxylase-1 activity and/or bone mineralization status. The bone formation and resorption markers, N-terminal propeptide and C-terminal telopeptide of Type 1 collagen, were both increased in Phospho1(-/-) mice and this we associated with increased bone remodeling during fracture repair or an attempt to remodel a mechanically competent bone capable of withstanding physiological load. In summary these data indicate that Phospho1(-/-) bones are hypomineralized and, consequently, are softer and more flexible. An inability to withstand physiological loading may explain the deformations noted. We hypothesize that this phenotype is due to the reduced availability of inorganic phosphate to form hydroxyapatite during mineralization, creating an undermineralized yet active bone. (C) 2011 Elsevier Inc. All rights reserved.