Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways

During bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium conce...

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Main Authors: Xiaohang Gao, Xiaohui Di, Jingjing Li, Yiting Kang, Wenjun Xie, Lijun Sun, Jianbao Zhang
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/5/4991
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author Xiaohang Gao
Xiaohui Di
Jingjing Li
Yiting Kang
Wenjun Xie
Lijun Sun
Jianbao Zhang
author_facet Xiaohang Gao
Xiaohui Di
Jingjing Li
Yiting Kang
Wenjun Xie
Lijun Sun
Jianbao Zhang
author_sort Xiaohang Gao
collection DOAJ
description During bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca<sup>2+</sup>]<sub>i</sub>) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca<sup>2+</sup>]<sub>i</sub> transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.
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spelling doaj.art-6b30896cc8df4bccb8bb477f649783492023-11-17T07:56:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01245499110.3390/ijms24054991Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism PathwaysXiaohang Gao0Xiaohui Di1Jingjing Li2Yiting Kang3Wenjun Xie4Lijun Sun5Jianbao Zhang6Key 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaInstitute of Sports Biology, Shaanxi Normal University, Xi’an 710119, ChinaKey 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, ChinaDuring bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca<sup>2+</sup>]<sub>i</sub>) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca<sup>2+</sup>]<sub>i</sub> transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.https://www.mdpi.com/1422-0067/24/5/4991calcium transientmetabolismproliferationosteoblasts
spellingShingle Xiaohang Gao
Xiaohui Di
Jingjing Li
Yiting Kang
Wenjun Xie
Lijun Sun
Jianbao Zhang
Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways
International Journal of Molecular Sciences
calcium transient
metabolism
proliferation
osteoblasts
title Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways
title_full Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways
title_fullStr Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways
title_full_unstemmed Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways
title_short Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways
title_sort extracellular calcium induced calcium transient regulating the proliferation of osteoblasts through glycolysis metabolism pathways
topic calcium transient
metabolism
proliferation
osteoblasts
url https://www.mdpi.com/1422-0067/24/5/4991
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