Molecular therapy, 2016-11, Vol.24 (11), p.1974-1986
2016
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- Autor(en) / Beteiligte
- Titel
- Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and Bone Cancer Pain
- Ist Teil von
- Molecular therapy, 2016-11, Vol.24 (11), p.1974-1986
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2016
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1525-0016eISSN: 1525-0024DOI: 10.1038/mt.2016.158Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5154475
- Format
- –
- Schlagworte
- Animals, Aptamers, Nucleotide - administration & dosage, Aptamers, Nucleotide - pharmacology, Arthritis, Experimental - drug therapy, Bone cancer, 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, Original, Osteoblasts - cytology, Osteoblasts - drug effects, Osteoporosis - drug therapy, Protein Binding - drug effects, Rats