RRC ID 62268
Author Jin L, Nonaka Y, Miyakawa S, Fujiwara M, Nakamura Y.
Title Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain.
Journal 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.
Volume 24(11)
Pages 1974-1986
Published 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
Human and Animal Cells MC3T3-E1(RCB1126)