Open AccessIntranuclear Actin Regulates Osteogenesis
Author(s) -
Sen Buer,
Xie Zhihui,
Uzer Gunes,
Thompson William R.,
Styner Maya,
Wu Xin,
Rubin Janet
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2090
Subject(s) - biology , runx2 , microbiology and biotechnology , cytochalasin d , phalloidin , actin , cofilin , mesenchymal stem cell , cytoskeleton , nuclear transport , actin remodeling , actin cytoskeleton , transcription factor , cell nucleus , cell , nucleus , gene , genetics
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. S tem C ells 2015;33:3065–3076