Intranuclear Actin Regulates Osteogenesis.
Stem Cells
; 33(10): 3065-76, 2015 Oct.
Article
in En
| MEDLINE
| ID: mdl-26140478
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteogenesis
/
Actin Cytoskeleton
/
Actins
/
Core Binding Factor Alpha 1 Subunit
/
Mesenchymal Stem Cells
Limits:
Animals
Language:
En
Journal:
Stem Cells
Year:
2015
Document type:
Article
Affiliation country:
United States