title: Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain.
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.
authors: Ribomic Inc., Tokyo, Japan.
authors: Ling
authors: L
authors: Jin
authors: Ribomic Inc., Tokyo, Japan.
authors: Yosuke
authors: Y
authors: Nonaka
authors: Ribomic Inc., Tokyo, Japan.
authors: Shin
authors: S
authors: Miyakawa
authors: Ribomic Inc., Tokyo, Japan.
authors: Masatoshi
authors: M
authors: Fujiwara
authors: Ribomic Inc., Tokyo, Japan; Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Electronic address: nak@ims.u-tokyo.ac.jp.
authors: Yoshikazu
authors: Y
authors: Nakamura
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy*; D000072716:Cancer Pain / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats
chemical_list: D052157:Aptamers, Nucleotide; D016222:Fibroblast Growth Factor 2