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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Mar 11

PMID 36902420

Authors

Xiaohang Gao

Xiaohui Di

Jingjing Li

Yiting Kang

Wenjun Xie

Lijun Sun

Jianbao Zhang

Affiliations

Soon will be listed here.

Abstract

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]) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca] 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.

Citing Articles

Ex Vivo, In Vitro and In Vivo Bone Health Properties of Grana Padano Cheese.

Martelli C, Ottobrini L, Ferraretto A, Bendinelli P, Cattaneo S, Masotti F Foods. 2025; 14(2).

PMID: 39856939 PMC: 11765351. DOI: 10.3390/foods14020273.

Vancomycin-Loaded Silk Fibroin/Calcium Phosphate/Methylcellulose-Based In Situ Thermosensitive Hydrogel: A Potential Function for Bone Regeneration.

Phewchan P, Laoruengthana A, Chomchalao P, Lamlertthon S, Tiyaboonchai W Gels. 2024; 10(11).

PMID: 39590051 PMC: 11594143. DOI: 10.3390/gels10110695.

Hyperglycosylation as an Indicator of Aging in the Bone Metabolome of .

Labeille R, Elliott J, Abdulla H, Seemann F Metabolites. 2024; 14(10).

PMID: 39452906 PMC: 11509322. DOI: 10.3390/metabo14100525.

ORAI Ca Channels in Cancers and Therapeutic Interventions.

Zhang Q, Wang C, He L Biomolecules. 2024; 14(4).

PMID: 38672434 PMC: 11048467. DOI: 10.3390/biom14040417.

References

Gao J, Feng Z, Wang X, Zeng M, Liu J, Han S . SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress. Cell Death Differ. 2017; 25(2):229-240. PMC: 5762839. DOI: 10.1038/cdd.2017.144. View

Taniguchi C, Tran T, Kondo T, Luo J, Ueki K, Cantley L . Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. Proc Natl Acad Sci U S A. 2006; 103(32):12093-7. PMC: 1524929. DOI: 10.1073/pnas.0604628103. View

Deliot N, Constantin B . Plasma membrane calcium channels in cancer: Alterations and consequences for cell proliferation and migration. Biochim Biophys Acta. 2015; 1848(10 Pt B):2512-22. DOI: 10.1016/j.bbamem.2015.06.009. View

Boudot C, Saidak Z, Boulanouar A, Petit L, Gouilleux F, Massy Z . Implication of the calcium sensing receptor and the Phosphoinositide 3-kinase/Akt pathway in the extracellular calcium-mediated migration of RAW 264.7 osteoclast precursor cells. Bone. 2010; 46(5):1416-23. DOI: 10.1016/j.bone.2010.01.383. View

Tao R, Sun H, Lau C, Tse H, Lee H, Li G . Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells. J Cell Mol Med. 2011; 15(12):2684-96. PMC: 4373437. DOI: 10.1111/j.1582-4934.2011.01263.x. View

Ma R, Gan L, Ren H, Harrison A, Qian J . PDK2-enhanced glycolysis promotes fibroblast proliferation in thyroid-associated ophthalmopathy. J Mol Endocrinol. 2020; 65(4):163-174. DOI: 10.1530/JME-20-0143. View

Li X, Sun X, Carmeliet P . Hallmarks of Endothelial Cell Metabolism in Health and Disease. Cell Metab. 2019; 30(3):414-433. DOI: 10.1016/j.cmet.2019.08.011. View

Shares B, Busch M, White N, Shum L, Eliseev R . Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation. J Biol Chem. 2018; 293(41):16019-16027. PMC: 6187642. DOI: 10.1074/jbc.RA118.004102. View

Tonelli F, Santos A, Gomes D, L da Silva S, Gomes K, Ladeira L . Stem cells and calcium signaling. Adv Exp Med Biol. 2012; 740:891-916. PMC: 3979962. DOI: 10.1007/978-94-007-2888-2_40. View

10.

Esen E, Chen J, Karner C, Okunade A, Patterson B, Long F . WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. Cell Metab. 2013; 17(5):745-55. PMC: 3653292. DOI: 10.1016/j.cmet.2013.03.017. View

11.

Ivanova H, Vervliet T, Missiaen L, Parys J, De Smedt H, Bultynck G . Inositol 1,4,5-trisphosphate receptor-isoform diversity in cell death and survival. Biochim Biophys Acta. 2014; 1843(10):2164-83. DOI: 10.1016/j.bbamcr.2014.03.007. View

12.

Hou M, Kuo H, Li J, Wang Y, Chang C, Chen K . Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells. Biochim Biophys Acta. 2011; 1810(12):1278-84. DOI: 10.1016/j.bbagen.2011.07.001. View

13.

Balaban R . The role of Ca(2+) signaling in the coordination of mitochondrial ATP production with cardiac work. Biochim Biophys Acta. 2009; 1787(11):1334-41. PMC: 3177847. DOI: 10.1016/j.bbabio.2009.05.011. View

14.

Ward P, Thompson C . Signaling in control of cell growth and metabolism. Cold Spring Harb Perspect Biol. 2012; 4(7):a006783. PMC: 3385956. DOI: 10.1101/cshperspect.a006783. View

15.

Gorvin C . Molecular and clinical insights from studies of calcium-sensing receptor mutations. J Mol Endocrinol. 2019; 63(2):R1-R16. DOI: 10.1530/JME-19-0104. View

16.

MUNYON W, MERCHANT D . The relation between glucose utilization, lactic acid production and utilization and the growth cycle of L strain fibroblasts. Exp Cell Res. 1959; 17(3):490-8. DOI: 10.1016/0014-4827(59)90069-2. View

17.

Quarles L, Yohay D, Lever L, Caton R, Wenstrup R . Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. J Bone Miner Res. 1992; 7(6):683-92. DOI: 10.1002/jbmr.5650070613. View

18.

Keinan D, Yang S, Cohen R, Yuan X, Liu T, Li Y . Role of regulator of G protein signaling proteins in bone. Front Biosci (Landmark Ed). 2014; 19(4):634-48. PMC: 3966557. DOI: 10.2741/4232. View

19.

Lee J, Liu R, Li J, Zhang C, Wang Y, Cai Q . Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis. Nat Commun. 2017; 8(1):949. PMC: 5643558. DOI: 10.1038/s41467-017-00906-9. View

20.

Boynton A, Whitfield J, Isaacs R, Morton H . Control of 3T3 cell proliferation by calcium. In Vitro. 1974; 10:12-7. DOI: 10.1007/BF02615333. View