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- Title
Intranuclear Actin Regulates Osteogenesis.
- Authors
Sen, Buer; Xie, Zhihui; Uzer, Gunes; Styner, Maya; Wu, Xin; Rubin, Janet; Thompson, William R.
- 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. S tem C ells 2015;33:3065-3076
- Subjects
MESENCHYMAL stem cells; CYTOSKELETON; OSTEOGENESIS imperfecta
- Publication
Stem Cells, 2015, Vol 33, Issue 10, p3065
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.2090