4.7 Article

Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis

Journal

Publisher

MDPI
DOI: 10.3390/ijms22126580

Keywords

lamin A; C; LINC; nucleoskeleton; nuclear envelope; adipogenesis; mechanical signals; mesenchymal stem cells

Funding

  1. NIH [AG059923, P20GM109095]
  2. NSF [1929188, 2025505, R01AR049069, AR075803]
  3. Career Development Award in Orthopedics Research
  4. Scientific and Technological Research Council of Turkey 2214-A
  5. Directorate For Engineering
  6. Div Of Civil, Mechanical, & Manufact Inn [2025505] Funding Source: National Science Foundation
  7. Office of Integrative Activities
  8. Office Of The Director [1929188] Funding Source: National Science Foundation

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Mesenchymal stem cells (MSCs) maintain musculoskeletal system by differentiating into osteoblasts and adipocytes. Mechanical signals like strain and low-intensity vibration regulate MSC differentiation via cell structure control. Lamin A/C protein is crucial for nuclear architecture, and its depletion affects adipogenesis markers and cellular stiffness. The study suggests mechanoregulation of adipogenesis and mechanical activation of focal adhesions happen independently from lamin A/C.
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.

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