Stem Cells. 2015 Jul 3. doi: 10.1002/stem.2090. [Epub ahead of print]

Intranuclear Actin Regulates Osteogenesis.

Sen B¹, Xie Z¹, Uzer G¹, Thompson WR^2,1, Styner M¹, Wu X¹, Rubin J¹.

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 (MSC), 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 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 one 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. This article is protected by copyright. All rights reserved.