Zinc Promotes Osteoblast Differentiation in Human Mesenchymal Stem Cells Via Activation of the cAMP-PKA-CREB Signaling Pathway

Stem Cells and Development
Kwang Hwan ParkJin Woo Lee

Abstract

The crucial trace element zinc stimulates osteogenesis in vitro and in vivo. However, the pathways mediating these effects remain poorly understood. This study aimed to investigate the effects of zinc on osteoblast differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs) and to identify the molecular mechanisms of these effects. In hBMSCs, zinc exposure resulted in a dose-dependent increase in osteogenesis and increased mRNA and protein levels of the master transcriptional factor RUNX2. Analyzing the upstream signaling pathways of RUNX2, we found that protein kinase A (PKA) signaling inhibition blocked zinc-induced osteogenic effects. Zinc exposure increased transcriptional activity and protein levels of phospho-CREB and enhanced translocation of phospho-CREB into the nucleus. These effects were reversed by H-89, a potent inhibitor of PKA. Moreover, zinc exposure led to dose-dependent increases in levels of intracellular cyclic adenosine monophosphate (cAMP). These findings indicate that zinc activates the PKA signaling pathway by triggering an increase in intracellular cAMP, leading to enhanced osteogenic differentiation in hBMSCs. Our results suggest that zinc exerts osteogenic effects in hBMSCs by activat...Continue Reading

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Citations

Nov 24, 2018·Biological Trace Element Research·Erin Gaffney-Stomberg
May 23, 2020·Journal of Biomedical Materials Research. Part a·Romina ShafaghiMark R Towler
May 16, 2020·Materials·J Patrick O'ConnorJessica A Cottrell
May 13, 2020·Archives of Toxicology·Christos T ChasapisMaria E Stefanidou
Sep 22, 2019·International Journal of Molecular Sciences·Kazunori HamamuraAkifumi Togari
Sep 10, 2020·International Journal of Nanomedicine·Yuehong LiYanguo Qin
Oct 31, 2020·Journal of Biomedical Materials Research. Part a·Daniella MarxMark Towler
Feb 14, 2021·Stem Cell Research & Therapy·Siyi WangYunsong Liu
Nov 6, 2020·Biological Trace Element Research·Azadeh Meshkini
Feb 2, 2021·Frontiers in Cell and Developmental Biology·Elia Bosch-RuéRoman A Perez
May 1, 2021·International Journal of Molecular Sciences·Santie LiKwang-Youl Lee
Aug 3, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Sana BoughammouraMartine Cohen Solal
Dec 24, 2020·ACS Applied Materials & Interfaces·Xiaomeng GaoQianbing Wan
Dec 16, 2020·ACS Biomaterials Science & Engineering·Vianni ChopraDeepa Ghosh

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Methods Mentioned

BETA
Assay
fluorescence-activated cell sorting
FACS
protein
electrophoresis
ELISA
flow cytometry
nuclear translocation
confocal microscopy

Software Mentioned

FlowJo
GraphPad PRISM
R

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