Lamin a/c is dispensable to mechanical repression of adipogenesis

Matthew Goelzer, Amel Dudakovic, Melis Olcum, Buer Sen, Engin Ozcivici, Janet Rubin, Andre J van Wijnen, Gunes Uzer

Research output: Contribution to journalArticlepeer-review

Abstract

Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.

Original languageEnglish (US)
Article number6580
JournalInternational journal of molecular sciences
Volume22
Issue number12
DOIs
StatePublished - Jun 2 2021

Keywords

  • Adipogenesis
  • Lamin A/C
  • LINC
  • Mechanical signals
  • Mesenchymal stem cells
  • Nuclear envelope
  • Nucleoskeleton

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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