Loss of β ‐Actin Leads to Accelerated Mineralization and Dysregulation of Osteoblast‐Differentiation Genes during Osteogenic Reprogramming

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Abstract: Actin plays fundamental roles in both the cytoplasm and the cell nucleus. In the nucleus, β‐actin regulates neuronal reprogramming by consolidating a heterochromatin landscape required for transcription of neuronal gene programs, yet it remains unknown whether it has a role in other differentiation models. To explore the potential roles of β‐actin in osteogenesis, β‐actin wild‐type (WT) and β‐actin knockout (KO) mouse embryonic fibroblasts (MEFs) are reprogrammed to osteoblast‐like cells using small molecules in vitro. It is discovered that loss of β‐actin leads to an accelerated mineralization phenotype (hypermineralization), accompanied with enhanced formation of extracellular hydroxyapatite microcrystals, which originate in the mitochondria in the form of microgranules. This phenotype is a consequence of rapid upregulation of mitochondrial genes including those involved in oxidative phosphorylation (OXPHOS) in reprogrammed KO cells. It is further found that osteogenic gene programs are differentially regulated between WT and KO cells, with clusters of genes exhibiting different temporal expression patterns. A novel function for β‐actin in osteogenic reprogramming through a mitochondria‐based mechanism that controls cell‐mediated mineralization is proposed.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Loss of β ‐Actin Leads to Accelerated Mineralization and Dysregulation of Osteoblast‐Differentiation Genes during Osteogenic Reprogramming ; volume:7 ; number:23 ; year:2020 ; extent:7
Advanced science ; 7, Heft 23 (2020) (gesamt 7)

Urheber
Gjorgjieva, Tamara
Xie, Xin
Commins, Patrick
Pasricha, Renu
Mahmood, Syed Raza
Gunsalus, Kristin C.
Naumov, Pance
Percipalle, Piergiorgio

DOI
10.1002/advs.202002261
URN
urn:nbn:de:101:1-2022062313093912368451
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:29 MESZ

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Beteiligte

  • Gjorgjieva, Tamara
  • Xie, Xin
  • Commins, Patrick
  • Pasricha, Renu
  • Mahmood, Syed Raza
  • Gunsalus, Kristin C.
  • Naumov, Pance
  • Percipalle, Piergiorgio

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