論文 - 詳細
| RRC ID | 62268 |
|---|---|
| 著者 | Jin L, Nonaka Y, Miyakawa S, Fujiwara M, Nakamura Y. |
| タイトル | Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain. |
| ジャーナル | Mol Ther |
| Abstract |
Fibroblast growth factor 2 (FGF2) plays a crucial role in bone remodeling and disease progression. However, the potential of FGF2 antagonists for treatment of patients with bone diseases has not yet been explored. Therefore, we generated a novel RNA aptamer, APT-F2, specific for human FGF2 and characterized its properties in vitro and in vivo. APT-F2 blocked binding of FGF2 to each of its four cellular receptors, inhibited FGF2-induced downstream signaling and cells proliferation, and restored osteoblast differentiation blocked by FGF2. APT-F2P, a PEGylated form of APT-F2, effectively blocked the bone disruption in mouse and rat models of arthritis and osteoporosis. Treatment with APT-F2P also exerted a strong analgesic effect, equivalent to morphine, in a mouse model of bone cancer pain. These findings demonstrated dual therapeutic action of APT-F2P in bone diseases and pain, providing a promising approach to the treatment of bone diseases. |
| 巻・号 | 24(11) |
| ページ | 1974-1986 |
| 公開日 | 2016-11-1 |
| DOI | 10.1038/mt.2016.158 |
| PII | S1525-0016(16)45453-5 |
| PMID | 27506449 |
| PMC | PMC5154475 |
| MeSH | Animals Aptamers, Nucleotide / administration & dosage* Aptamers, Nucleotide / pharmacology Arthritis, Experimental / drug therapy* Cancer Pain / drug therapy* Cell Differentiation / drug effects Cell Proliferation / drug effects Cell Survival / drug effects Disease Models, Animal Fibroblast Growth Factor 2 / antagonists & inhibitors* Fibroblast Growth Factor 2 / metabolism Humans MAP Kinase Signaling System / drug effects Mice NIH 3T3 Cells Osteoblasts / cytology Osteoblasts / drug effects* Osteoporosis / drug therapy* Protein Binding / drug effects Rats |
| IF | 8.986 |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-E1(RCB1126) |