Reference - Detail
RRC ID | 44498 |
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Author | Onishi M, Fujita Y, Yoshikawa H, Yamashita T. |
Title | Inhibition of Rac1 promotes BMP-2-induced osteoblastic differentiation. |
Journal | Cell Death Dis |
Abstract |
Small G proteins of the Rho family are pivotal regulators of several signaling networks. The Ras homolog family (Rho) and one of its targets, Rho-associated protein kinase (ROCK), participate in a wide variety of biological processes, including bone formation. A previous study has demonstrated that the ROCK inhibitor Y-27632 enhanced bone formation induced by recombinant human bone morphogenetic protein-2 (BMP-2) in vivo and in vitro. However, the effect of other Rho family members, such as Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42), on bone formation remains unknown. In this study, we investigated whether Rac1 also participates in BMP-2-induced osteogenesis. Expression of a dominant-negative mutant of Rac1 enhanced BMP-2-induced osteoblastic differentiation in C2C12 cells, whereas a constitutively active mutant of Rac1 attenuated that effect. Knockdown of T-lymphoma invasion and metastasis 1 (Tiam1), a Rac-specific guanine nucleotide exchange factor, enhanced BMP-2-induced alkaline phosphatase activity. Further, we demonstrated that BMP-2 stimulated Rac1 activity. These results indicate that the activation of Rac1 attenuates osteoblastic differentiation in C2C12 cells. |
Volume | 4(6) |
Pages | e698 |
Published | 2013-6-27 |
DOI | 10.1038/cddis.2013.226 |
PII | cddis2013226 |
PMID | 23807227 |
PMC | PMC3702300 |
MeSH | Alkaline Phosphatase / metabolism Aminoquinolines / pharmacology Animals Biomarkers / metabolism Bone Morphogenetic Protein 2 / physiology* Cell Differentiation* Cell Line Core Binding Factor Alpha 1 Subunit / metabolism Enzyme Activation Gene Knockdown Techniques Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism Humans Mice Neuropeptides / antagonists & inhibitors Neuropeptides / genetics* Neuropeptides / metabolism Osteoblasts / physiology* Osteocalcin / metabolism Osteogenesis Pyrimidines / pharmacology Signal Transduction Smad Proteins / metabolism T-Lymphoma Invasion and Metastasis-inducing Protein 1 rac1 GTP-Binding Protein / antagonists & inhibitors rac1 GTP-Binding Protein / genetics* rac1 GTP-Binding Protein / metabolism |
IF | 6.304 |
Times Cited | 22 |
WOS Category | CELL BIOLOGY |
Resource | |
Human and Animal Cells | C2C12(RCB0987) MC3T3-E1(RCB1126) |