Researchers find Citrate Metabolism and Deposition during Bone Remodeling
Citrate is presented in vertebrate bone universally as an integral part of apatite nanocomposite which is important for bone structure and its stability. However, the source of the citrate in bone is not clearly known, in particular, how the intracellular citrate metabolism and its deposition is governed during apatite formation is not well defined.
A joint research group of Prof. GUAN Min from Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences and Prof. WANG Junfeng from High Magnetic Field Laboratory, Chinese Academy of Sciences reports that during osteoblast genesis of mesenchymal stem cells (MSC), the citrate is produced as a key intermediate in mitochondrial tricarboxylic acid cycle, and further deposited in bone apatite.
The authors found that the citrate of bone apatite was produced by mineralized MSC by tracing with stable isotopically labeled carbon. Moreover, they demonstrated that zinc-Runx2/Osterix-ZIP1 regulation axis promotes osteoblast differentiation and apatite formation, uncover mitochondrial citrate metabolism and its relationship with zinc homeostasis during bone remodeling. Their findings highlight the mitochondrial and the metabolic changes not only meets higher amounts of energy demand during osteogenic differentiation of MSC, but also provides metabolic intermediates directly participating in bone formation.
The paper entitled “Runx2/Osterix and Zinc Uptake Synergize to Orchestrate Osteogenic Differentiation and Citrate containing Bone Apatite Formation” has been published in Advanced Science.
This work was supported by the National Natural Science Foundation of China Grant, Ministry of Science and Technology of China, Youth Innovation Promotion Association of Chinese Academy of Sciences, Shenzhen Science and Technology Research Funding and Shenzhen Peacock Program.
Fig. Diagram of Zn2+ induced osteoblast differentiation of MSCs and citrate deposition during bone remodeling. (Image by Prof. GUAN Min )