Osterix and Zinc Uptake Synergize to Orchestrate Osteogenic Differentiation and Citrate Containing-bone Apatite Formation
文献类型：会议论文
| 作者 | Xuekun Fu; Tongling Huang; Min Guan |
| 出版日期 | 2017 |
| 会议日期 | 2017 |
| 会议地点 | 湖南吉首 |
| 英文摘要 | Citrate is found strongly bound to apatite nanocrystals in bone. However, little is known about the source of bone apatite citrate, intracellular citrate metabolism and its deposition. Differentiation and mineralization during osteoblastogenesis of mesenchymal stem cells (MSCs) are requisites to building bone. By using radiolabeled glucose ((U- 13 C6)-Glucose) as a source and detecting citrate in-situ by solid-state cross-polarization NMR, we demonstrated that citrate is deposited within calcified extracellular matrix (ECM) and the source of citrate is derived from glucose metabolized by the osteogenic MSCs. Zinc is known to favor citrate production by inhibiting m-aconitase, an enzyme responsible for mitochondrial citrate oxidation. We thus examined expression levels of several metal zinc-ion transporters implicated in bone formation and found that ZIP1 expression level was markedly increased upon MSC osteogenesis. By using luciferase reporters and chromatin immunoprecipitation assays, we demonstrated that Osterix transcriptionally controls ZIP1 expression through bona fide Osterix binding sites in the ZIP1 promoter. Moreover, ZIP1 is required for BMP2/Osterix signaling to promote osteogenesis and citrate deposition. Importantly, citrate concentration showed similar trend with Ca 2+ and Zn 2+ in the bone marrow and bone matrix of mice at different ages. However, Ca 2+ and citrate deposited in ECM was significantly enhanced with rescued ZIP1 expression or Zn 2+ supplement in MSCs isolated from aged mice. Taken together, our results indicate zinc-Osterix-ZIP1 regulation axis forms a positive feed-forward loop that promotes differentiation of MSCs; our observations further uncover mitochondrial citrate metabolism participation in calcified ECM deposition and its relationship with zinc homeostasis during bone mineralization and formation. Our findings provide fresh insight into the fundamental understanding of the association of zinc, citrate and bone mineralization, and may have important implications for understanding and treating pathological bone mineralization. |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/12424]  |
| 专题 | 深圳先进技术研究院_医药所 |
| 作者单位 | 2017 |
| 推荐引用方式 GB/T 7714 | Xuekun Fu,Tongling Huang,Min Guan. Osterix and Zinc Uptake Synergize to Orchestrate Osteogenic Differentiation and Citrate Containing-bone Apatite Formation[C]. 见:. 湖南吉首. 2017. |
入库方式： OAI收割
来源：深圳先进技术研究院
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