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Sen B
; Xie Z
; Uzer G
; Thompson WR
; Styner M
; Wu X
; Rubin J
Stem Cells
2015[Oct]; 33
(10
): 3065-76
PMID26140478
show ga
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.
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