| RRC ID |
19304
|
| 著者 |
Takayama K, Suzuki A, Manaka T, Taguchi S, Hashimoto Y, Imai Y, Wakitani S, Takaoka K.
|
| タイトル |
RNA interference for noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro.
|
| ジャーナル |
J Bone Miner Metab
|
| Abstract |
Noggin is a major extracellular antagonist to bone morphogenetic proteins (BMPs) which binds to BMPs and blocks binding of them to BMP-specific receptors and negatively regulates BMP-induced osteoblastic differentiation. In this study, we investigated the effect of noggin silencing by transfection of small interfering RNA (siRNA) on BMP-induced osteoblastic differentiation in vitro and ectopic bone formation in vivo induced by recombinant human BMP-2 (rhBMP-2). Noggin mRNA expression was up-regulated in response to rhBMP-2 in C2C12 cells, a myoblastic cell line, in dose- and time-dependent fashion as determined by real-time RT-PCR assay. Silencing of noggin expression by transfection of noggin siRNA suppressed BMP-stimulated noggin expression, resulting in acceleration of BMP-induced osteoblastic differentiation. For in vivo noggin silencing, siRNA was injected locally into back muscles and transfected into local cells by electroporation, where rhBMP-2-retaining (5 microg) collagen disks had been surgically placed. The implants were harvested at 2 weeks after surgery from experimental and control group mice and analyzed by radiological and histological methods. As a result, bone mineral content of ossicles ectopically induced by rhBMP-2 was significantly increased by silencing of noggin. Our findings suggest that silencing of noggin enhances the osteoblastic differentiation of BMP-responding cells in vitro and new bone formation induced by rhBMP-2 in vivo by eliminating negative regulation of the effects of BMP. RNA interference might be useful for intensifying the effects of BMP in promoting new bone (callus) formation in repair of damaged bone.
|
| 巻・号 |
27(4)
|
| ページ |
402-11
|
| 公開日 |
2009-1-1
|
| DOI |
10.1007/s00774-009-0054-x
|
| PMID |
19252814
|
| MeSH |
Absorbable Implants
Absorptiometry, Photon
Alkaline Phosphatase / metabolism
Animals
Bone Density / drug effects
Bone Morphogenetic Protein 2 / administration & dosage
Bone Morphogenetic Protein 2 / pharmacology
Bone Morphogenetic Proteins / administration & dosage
Bone Morphogenetic Proteins / pharmacology*
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cell Differentiation / drug effects*
Cell Line
Collagen
Electroporation
Gene Expression / drug effects
Gene Expression / genetics
Humans
Mice
Mice, Inbred ICR
Muscle, Skeletal / cytology
Muscle, Skeletal / drug effects
Muscle, Skeletal / metabolism
Myoblasts / cytology
Myoblasts / drug effects
Myoblasts / metabolism
Osteoblasts / cytology*
Osteoblasts / drug effects
Osteoblasts / metabolism
Osteocalcin / genetics
Osteogenesis / drug effects*
RNA Interference*
RNA, Small Interfering / genetics
Recombinant Proteins / administration & dosage
Recombinant Proteins / pharmacology
Transfection
|
| IF |
2.297
|
| 引用数 |
48
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987) |
