The epigenetic mechanism of mechanically induced osteogenic differentiation

Emily J. Arnsdorf, Padmaja Tummala, Alesha Castillo, Fan Zhang, Christopher R. Jacobs

Research output: Contribution to journalArticle

Abstract

Epigenetic regulation of gene expression occurs due to alterations in chromatin proteins that do not change DNA sequence, but alter the chromatin architecture and the accessibility of genes, resulting in changes to gene expression that are preserved during cell division. Through this process genes are switched on or off in a more durable fashion than other transient mechanisms of gene regulation, such as transcription factors. Thus, epigenetics is central to cellular differentiation and stem cell linage commitment. One such mechanism is DNA methylation, which is associated with gene silencing and is involved in a cell's progression towards a specific fate. Mechanical signals are a crucial regulator of stem cell behavior and important in tissue differentiation; however, there has been no demonstration of a mechanism whereby mechanics can affect gene regulation at the epigenetic level. In this study, we identified candidate DNA methylation sites in the promoter regions of three osteogenic genes from bone marrow derived mesenchymal stem cells (MSCs). We demonstrate that mechanical stimulation alters their epigenetic state by reducing DNA methylation and show an associated increase in expression. We contrast these results with biochemically induced differentiation and distinguish expression changes associated with durable epigenetic regulation from those likely to be due to transient changes in regulation. This is an important advance in stem cell mechanobiology as it is the first demonstration of a mechanism by which the mechanical micro-environment is able to induce epigenetic changes that control osteogenic cell fate, and that can be passed to daughter cells. This is a first step to understanding that will be vital to successful bone tissue engineering and regenerative medicine, where continued expression of a desired long-term phenotype is crucial.

Original languageEnglish (US)
Pages (from-to)2881-2886
Number of pages6
JournalJournal of Biomechanics
Volume43
Issue number15
DOIs
StatePublished - Nov 16 2010

Fingerprint

Stem cells
Epigenomics
Gene expression
Genes
DNA Methylation
Bone
Demonstrations
Stem Cells
Chromatin
Transcription factors
DNA sequences
Tissue engineering
Biophysics
Mechanics
Regenerative Medicine
Cells
Gene Expression Regulation
Gene Silencing
Tissue Engineering
Tissue

Keywords

  • Epigenetic
  • Mechanotransduction
  • Mesenchymal stem cell
  • Osteogenic differentiation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rehabilitation
  • Biophysics
  • Biomedical Engineering

Cite this

The epigenetic mechanism of mechanically induced osteogenic differentiation. / Arnsdorf, Emily J.; Tummala, Padmaja; Castillo, Alesha; Zhang, Fan; Jacobs, Christopher R.

In: Journal of Biomechanics, Vol. 43, No. 15, 16.11.2010, p. 2881-2886.

Research output: Contribution to journalArticle

Arnsdorf, Emily J. ; Tummala, Padmaja ; Castillo, Alesha ; Zhang, Fan ; Jacobs, Christopher R. / The epigenetic mechanism of mechanically induced osteogenic differentiation. In: Journal of Biomechanics. 2010 ; Vol. 43, No. 15. pp. 2881-2886.
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