Vibration induced osteogenic commitment of mesenchymal stem cells is enhanced by cytoskeletal remodeling but not fluid shear

Gunes Uzer, Suphannee Pongkitwitoon, M. Ete Chan, Stefan Judex

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Consistent across studies in humans, animals and cells, the application of vibrations can be anabolic and/or anti-catabolic to bone. The physical mechanisms modulating the vibration-induced response have not been identified. Recently, we developed an in vitro model in which candidate parameters including acceleration magnitude and fluid shear can be controlled independently during vibrations. Here, we hypothesized that vibration induced fluid shear does not modulate mesenchymal stem cell (MSC) proliferation and mineralization and that cell's sensitivity to vibrations can be promoted via actin stress fiber formation. Adipose derived human MSCs were subjected to vibration frequencies and acceleration magnitudes that induced fluid shear stress ranging from 0.04. Pa to 5. Pa. Vibrations were applied at magnitudes of 0.15. g, 1. g, and 2. g using frequencies of both 100. Hz and 30. Hz. After 14. d and under low fluid shear conditions associated with 100. Hz oscillations, mineralization was greater in all vibrated groups than in controls. Greater levels of fluid shear produced by 30. Hz vibrations enhanced mineralization only in the 2. g group. Over 3. d, vibrations led to the greatest increase in total cell number with the frequency/acceleration combination that induced the smallest level of fluid shear. Acute experiments showed that actin remodeling was necessary for early mechanical up-regulation of RUNX-2 mRNA levels. During osteogenic differentiation, mechanically induced up-regulation of actin remodeling genes including Wiskott-Aldrich syndrome (WAS) protein, a critical regulator of Arp2/3 complex, was related to the magnitude of the applied acceleration but not to fluid shear. These data demonstrate that fluid shear does not regulate vibration induced proliferation and mineralization and that cytoskeletal remodeling activity may play a role in MSC mechanosensitivity.

Original languageEnglish
Pages (from-to)2296-2302
Number of pages7
JournalJournal of Biomechanics
Volume46
Issue number13
DOIs
StatePublished - 3 Sep 2013

Keywords

  • Bone
  • Differentiation
  • In vitro cell culture
  • Mechanical signals
  • Mesenchymal stem cells
  • Proliferation
  • Vibrations

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