Intranuclear Actin Regulates Osteogenesis.

Academic Article

Abstract

  • Depolymerization of the actin cytoskeleton induces nuclear trafficking of regulatory proteins and global effects on gene transcription. We here show that in mesenchymal stem cells (MSCs), cytochalasin D treatment causes rapid cofilin-/importin-9-dependent transfer of G-actin into the nucleus. The continued presence of intranuclear actin, which forms rod-like structures that stain with phalloidin, is associated with induction of robust expression of the osteogenic genes osterix and osteocalcin in a Runx2-dependent manner, and leads to acquisition of osteogenic phenotype. Adipogenic differentiation also occurs, but to a lesser degree. Intranuclear actin leads to nuclear export of Yes-associated protein (YAP); maintenance of nuclear YAP inhibits Runx2 initiation of osteogenesis. Injection of cytochalasin into the tibial marrow space of live mice results in abundant bone formation within the space of 1 week. In sum, increased intranuclear actin forces MSC into osteogenic lineage through controlling Runx2 activity; this process may be useful for clinical objectives of forming bone.
  • Published In

  • STEM CELLS  Journal
  • Keywords

  • Bone, Cofilin, Cytoskeleton, Importin 9, Mesenchymal stem cells, Runx2, Yes-associated protein, Actin Cytoskeleton, Actin Depolymerizing Factors, Actins, Animals, Cell Lineage, Cell Nucleus, Core Binding Factor Alpha 1 Subunit, Cytochalasin D, Mesenchymal Stem Cells, Mice, Osteogenesis, Phalloidine, Protein Transport
  • Digital Object Identifier (doi)

    Author List

  • Sen B; Xie Z; Uzer G; Thompson WR; Styner M; Wu X; Rubin J
  • Start Page

  • 3065
  • End Page

  • 3076
  • Volume

  • 33
  • Issue

  • 10