Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain

Mol Ther. 2016 Nov;24(11):1974-1986. doi: 10.1038/mt.2016.158. Epub 2016 Aug 10.


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.

MeSH terms

  • 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


  • Aptamers, Nucleotide
  • Fibroblast Growth Factor 2