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Stem Cells. 2015 Oct;33(10):3065-76. doi: 10.1002/stem.2090.

Intranuclear Actin Regulates Osteogenesis.

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Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Department of Physical Therapy, University of Indiana-Purdue, Indianapolis, Indiana.


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.


Bone; Cofilin; Cytoskeleton; Importin 9; Mesenchymal stem cells; Runx2; Yes-associated protein

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