AUTHOR=Hirakata Kazushi , Hiyama Miyabi , Itabashi Hideyuki , Uchiyama Akihiko , Motegi Sei-Ichiro 

TITLE=Modulation of keratinocyte proliferation, migration, and differentiation by calcium and magnesium

JOURNAL=Journal of Cutaneous Immunology and Allergy

VOLUME=Volume 8 - 2025

YEAR=2025

URL=https://www.frontierspartnerships.org/journals/journal-of-cutaneous-immunology-and-allergy/articles/10.3389/jcia.2025.15491

DOI=10.3389/jcia.2025.15491

ISSN=2574-4593

ABSTRACT=BackgroundCalcium and magnesium are essential ions that regulate multiple functions of keratinocytes. However, their precise effects on keratinocyte behavior remain incompletely understood.ObjectivesTo investigate the effects of varying calcium and magnesium concentrations on cell proliferation, migration, and the expression of genes related to differentiation and skin hydration in keratinocytes.MethodsHaCaT cells were stimulated by culture media with various calcium (0.32–18.0 mM) and magnesium concentrations (0.28–8.11 mM). MTT Assay was performed for proliferation. Cell migration ability was observed for 24 h using culture-Insert 2 well. mRNA levels of differentiation-associated gene expression was examined by qPCR assay.ResultsCompared to standard DMEM, lower calcium concentrations and higher magnesium concentrations promoted keratinocyte proliferation. The combination of low calcium and high magnesium additively enhanced cell migration. However, both conditions tended to suppress the expression of genes related to differentiation and moisture retention.ConclusionKeratinocyte functions related to proliferation, migration, and differentiation are intricately regulated by the concentrations of calcium and magnesium, as well as their interactions. Lower calcium and higher magnesium medium might have potential to enhance proliferation and migration in keratinocytes. However, further investigations under in vivo conditions are required to evaluate their effects and to translate these findings into clinical applications.