Level D· Scientific groundwork from lab and animal studiesLaboratory StudyEurope PMCOpen access

Citrate Mediates Crosstalk between Mitochondria and the Nucleus to Promote Human Mesenchymal Stem Cell In Vitro Osteogenesis

Morganti C., Bonora M., Marchi S., Ferroni L., Ferroni L., Gardin C.

Laboratory Study, published in Cells (2020) — summary generated from the PubMed abstract.

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Level D· Scientific groundwork from lab and animal studiesEvidence level of this study

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

  • Level A · Stronger Clinical Evidence
  • Level B · Emerging clinical evidence with positive signals
  • Level C · Early human research exploring benefits
  • Level D · Scientific groundwork from lab and animal studies
  • Emerging · Emerging topic under active research
Read the A–D evidence level guide

This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.

Study type
Laboratory Study
Journal
Cells (2020)
Reported sample size
—
Source database
Europe PMC
PMID
32326298
PMCID
PMC7226543
DOI
10.3390/cells9041034
Citations
32

Abstract (original English)

Citrate, generated in the mitochondria, is a key metabolite that might link metabolism with signaling, chromatin structure and transcription to orchestrate mesenchymal stem cells (MSCs) fate determination. Based on a detailed morphological analysis of 3D reconstruction of mitochondria and nuclei in single cells, we identified contact sites between these organelles that drastically increase in volume and number during the early stage of mesenchymal stem cell differentiation. These contact sites create a microdomain that facilitates exchange of signals from mitochondria to the nucleus. Interestingly, we found that the citrate derived from mitochondria is necessary for osteogenic lineage determination. Indeed, inhibition of the citrate transporter system dramatically affected osteogenesis, reduced citrate levels that could be converted in α-ketoglutarate, and consequently affected epigenetic marker H3K9me3 associated with the osteogenesis differentiation process. These findings highlight that mitochondrial metabolites play key regulatory roles in the MSCs differentiation process. Further in-depth investigation is needed to provide novel therapeutic strategies in the field of regenerative medicine .

What this study does not prove

  • • This study does not prove SVF is an approved treatment or a replacement for standard care.
  • • This is preclinical work; animal or laboratory results cannot be applied to humans.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

How we grade evidence
Cells, CulturedCell NucleusMitochondriaMesenchymal Stem CellsHumansKetoglutaric AcidsCitric AcidMembrane Transport ProteinsCell DifferentiationBiological Transport

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