論文 - 詳細
| RRC ID | 6599 |
|---|---|
| 著者 | Yoshikawa H, Yoshioka K, Nakase T, Itoh K. |
| タイトル | Stimulation of ectopic bone formation in response to BMP-2 by Rho kinase inhibitor: a pilot study. |
| ジャーナル | Clin Orthop Relat Res |
| Abstract |
The small GTPase Rho and Rho-associated protein kinase (Rho kinase, ROCK) signal participates in a variety of biological functions including vascular contraction, tumor invasion, and penile erection. Evidence also suggests Rho-ROCK is involved in signaling for mesenchymal cellular differentiation. However, whether it is involved in osteoblastic differentiation is unknown. We therefore asked whether Rho-ROCK signaling participates in recombinant human bone morphogenetic protein (rhBMP-2)-induced osteogenesis both in vitro and in vivo. Continuous delivery of a specific ROCK inhibitor (Y-27632) enhanced ectopic bone formation induced by rhBMP-2 impregnated into an atelocollagen carrier in mice without affecting systemic bone metabolism. Treatment with Y-27632 also enhanced the osteoblastic differentiation of cultured murine neonatal calvarial cells. These effects were associated with increased expression of BMP-4 gene. Expression of a dominant negative mutant of ROCK in ST2 cells promoted osteoblastic differentiation, while a constitutively active mutant of ROCK attenuated osteoblastic differentiation and the ROCK inhibitor reversed this phenotype. Thus, ROCK inhibits osteogenesis, and a ROCK inhibitor in combination with the local delivery of rhBMP/collagen composite may be clinically applicable for stimulating bone formation. |
| 巻・号 | 467(12) |
| ページ | 3087-95 |
| 公開日 | 2009-12-1 |
| DOI | 10.1007/s11999-009-0976-6 |
| PMID | 19609629 |
| PMC | PMC2772944 |
| MeSH | Amides / administration & dosage* Animals Animals, Newborn Bone Morphogenetic Protein 2 / administration & dosage* Bone Morphogenetic Protein 4 / genetics Cell Differentiation / drug effects Cell Movement / drug effects Cells, Cultured Collagen Dose-Response Relationship, Drug Drug Carriers Humans Male Mice Mice, Inbred ICR Mutation Ossification, Heterotopic / chemically induced* Ossification, Heterotopic / enzymology Ossification, Heterotopic / physiopathology Osteoblasts / drug effects* Osteoblasts / enzymology Osteogenesis / drug effects* Pilot Projects Protein Kinase Inhibitors / administration & dosage* Pyridines / administration & dosage* RNA, Messenger / metabolism Recombinant Proteins / administration & dosage Skull / drug effects Skull / enzymology Stromal Cells / drug effects Stromal Cells / enzymology Transfection rho-Associated Kinases / antagonists & inhibitors* rho-Associated Kinases / genetics rho-Associated Kinases / metabolism |
| IF | 4.329 |
| 引用数 | 30 |
| WOS 分野 | SURGERY ORTHOPEDICS |
| リソース情報 | |
| ヒト・動物細胞 | ST2(RCB0224) |