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Extracellular ATP-induced calcium oscillations regulating the differentiation of osteoblasts through aerobic oxidation metabolism pathways

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

The increase of ATP concentration in the extracellular space represents one of the effective signals that stimulate the physiological activities of cells when the bone is exposed to external mechanical stimulation such as stretching and shear stress force throughout life. However, the effects of ATP on osteoblast differentiation and related mechanisms are not well understood.

Materials and Methods

In this study, the roles of extracellular ATP on osteoblast differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated.

Results

Our results showed that 100 μM extracellular ATP initiated intracellular calcium ([Ca2+]i) oscillations via the calcium-sensing receptor (P2R) and promoted the differentiation of MC3T3-E1 cells. Metabolomics analysis showed that the differentiation of MC3T3-E1 cells depended on aerobic oxidation, but little glycolysis. Moreover, the differentiation of MC3T3-E1 cells and aerobic oxidation were suppressed with the inhibition of AMP-activated protein kinase (AMPK).

Conclusion

These results indicate that calcium oscillations triggered by extracellular ATP can activate aerobic oxidation through AMPK-related signaling pathways and thus promote osteoblast differentiation.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 11872297 and No. 31670954).

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Authors and Affiliations

  1. Key Laboratory of Biomedical Information Engineering of Education Ministry, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 711049, China

    Xiaohang Gao, Xiaohui Di, Jingjing Li, Yiting Kang, Wenjun Xie & Jianbao Zhang

  2. Institute of Sports Biology, Shaanxi Normal University, Xi’an, 710119, China

    Lijun Sun

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  1. Xiaohang Gao
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Contributions

JZ conceived and designed the research; XG, YK, and JL performed the experiments; XG, XD, and JL contributed to sample preparation and data analysis; LS, XD, and JL contributed to the interpretation of the results; XG wrote the original draft; WX and LS helped supervise the project and reviewed draft; JZ reviewed draft, acquired funding, and administrated the project. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Lijun Sun or Jianbao Zhang.

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Gao, X., Di, X., Li, J. et al. Extracellular ATP-induced calcium oscillations regulating the differentiation of osteoblasts through aerobic oxidation metabolism pathways. J Bone Miner Metab 41, 606–620 (2023). https://doi.org/10.1007/s00774-023-01449-4

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