Abstract
As the primary step for 'drug repositioning', we evaluated the effect of 2000 drugs and drug candidates on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP)-2 and found that butamben enhanced BMP-2-stimulated induction of alkaline phosphatase, a biomarker of osteoblastogenesis. Investigating the underlying mechanism of its anabolic actions, we found anabolic action of its derivative (compound 4) relies on BMP-2 signaling and mRNA induction of BMPs and voltage-gated potassium channels.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
4-Aminobenzoic Acid / chemistry
-
4-Aminobenzoic Acid / pharmacology
-
Alkaline Phosphatase / metabolism
-
Animals
-
Benzocaine / analogs & derivatives*
-
Benzocaine / chemistry
-
Benzocaine / pharmacology
-
Bone Morphogenetic Protein 2 / genetics
-
Bone Morphogenetic Protein 2 / metabolism*
-
Cell Differentiation / drug effects
-
Cell Line
-
Gene Expression Regulation / drug effects
-
Mice
-
Osteoblasts / cytology
-
Osteoblasts / drug effects
-
Osteoblasts / metabolism*
-
Potassium Channels, Voltage-Gated / metabolism*
-
RNA, Messenger / metabolism
-
Signal Transduction
-
para-Aminobenzoates*
Substances
-
Bone Morphogenetic Protein 2
-
Potassium Channels, Voltage-Gated
-
RNA, Messenger
-
para-Aminobenzoates
-
Alkaline Phosphatase
-
butamben
-
4-Aminobenzoic Acid
-
Benzocaine