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

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

  • J Bone Miner Metab. 2023 Jul 7. doi: 10.1007/s00774-023-01449-4.
Xiaohang Gao 1,  Xiaohui Di 1,  Jingjing Li 1,  Yiting Kang 1,  Wenjun Xie 1,  Lijun Sun 2,  Jianbao Zhang 3
Affiliations

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.
  • 2 Institute of Sports Biology, Shaanxi Normal University, Xi'an, 710119, China. [email protected].
  • 3 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. [email protected].
PMID: 37418073 DOI: 10.1007/s00774-023-01449-4
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.

Keywords

Calcium oscillations; Differentiation; Metabolism; Osteoblasts.

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