Runx2/Osterix and Zinc Uptake Synergize to Orchestrate Osteogenic Differentiation and Citrate Containing Bone Apatite Formation.
Runx2/Osterix and Zinc Uptake Synergize to Orchestrate Osteogenic Differentiation and Citrate Containing Bone Apatite Formation.
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Runx2/Osterix 和锌摄取协同协调成骨分化和含柠檬酸盐的骨磷灰石形成
DOI：
10.1002/advs.201700755
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Guan M
中科院分区：
文献类型：
--
作者：
Fu X;Li Y;Huang T;Yu Z;Ma K;Yang M;Liu Q;Pan H;Wang H;Wang J;Guan M
柠檬酸盐对骨的生物矿化是必不可少的，尤其是作为磷灰石纳米复合材料的组成部分。柠檬酸盐析出的磷灰石可能来源于间充质干细胞分化为成熟的成骨细胞。基于固态多核磁共振分析确定的13C标记信号，增强的线粒体活性和三羧酸循环中间体的碳源补充协调推进线粒体合成代谢和柠檬酸的沉积。此外，锌离子还具有双重功能：(1)锌离子内流受ZIP1的影响，而ZIP1受Runx2和Osterix的调控，形成促进成骨分化的锌-Runx2/Osterix-ZIP1调节轴；(2)锌离子促进柠檬酸在骨磷灰石中的蓄积和沉积。此外，与年龄相关的骨丢失与锌离子和柠檬酸的动态平衡有关；然而，锌离子摄取的恢复可以缓解与年龄相关的成骨能力和柠檬酸沉降量的下降。综上所述，这些结果表明，柠檬酸不仅是满足MSCs分化所需能量的关键代谢中间体，而且还参与了细胞外基质的矿化，从机制上深入了解了锌离子的动态平衡和骨形成。
Citrate is essential to biomineralization of the bone especially as an integral part of apatite nanocomposite. Citrate precipitate of apatite is hypothesized to be derived from mesenchymal stem/stromal cells (MSCs) upon differentiation into mature osteoblasts. Based on 13C‐labeled signals identified by solid‐state multinuclear magnetic resonance analysis, boosted mitochondrial activity and carbon‐source replenishment of tricarboxylic acid cycle intermediates coordinate to feed forward mitochondrial anabolism and deposition of citrate. Moreover, zinc (Zn2+) is identified playing dual functions: (i) Zn2+ influx is influenced by ZIP1 which is regulated by Runx2 and Osterix to form a zinc‐Runx2/Osterix‐ZIP1 regulation axis promoting osteogenic differentiation; (ii) Zn2+ enhances citrate accumulation and deposition in bone apatite. Furthermore, age‐related bone loss is associated with Zn2+ and citrate homeostasis; whereas, restoration of Zn2+ uptake alleviates age‐associated declining osteogenic capacity and amount of citrate deposition. Together, these results indicate that citrate is not only a key metabolic intermediate meeting the emerging energy demand of differentiating MSCs but also participates in extracellular matrix mineralization, providing mechanistic insight into Zn2+ homeostasis and bone formation.
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DOI：
10.1073/pnas.1208916109
发表时间：
2012-08-28
影响因子：
11.1
作者：
Boonrungsiman, Suwimon;Gentleman, Eileen;Stevens, Molly M.
通讯作者：
Stevens, Molly M.
影响因子：
2.4
作者：
Kim, Jung-Tak;Baek, Sang-Heum;Shin, Hong-In
通讯作者：
Shin, Hong-In
衰老会减少 ERRα 引导的线粒体谷氨酰胺酶表达，从而抑制谷氨酰胺回补和间充质干细胞的成骨分化。
影响因子：
5.2
作者：
Huang, Tongling;Liu, Renzhong;Guan, Min
通讯作者：
Guan, Min
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.8
作者：
Hassan, Mohammad Q.;Tare, Rahul S.;Lian, Jane B.
通讯作者：
Lian, Jane B.