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Updated: Jul 13, 2026

Covalent Binding of BMP-2 on Surfaces Using a Self-assembled Monolayer Approach
Published on: August 26, 2013
Role of RGM coreceptors in bone morphogenetic protein signaling
Peter J Halbrooks1, Ru Ding, John M Wozney
1Quality Control Technical Services Laboratory, Genzyme Corporation, Framingham MA, 01701, USA. Peter.Halbrooks@genzyme.com
Background:
The repulsive guidance molecule (RGM) proteins, originally discovered for their roles in neuronal development, have been recently identified as co-receptors in the bone morphogenetic protein (BMP) signaling pathway. BMPs are members of the TGFbeta superfamily of signaling cytokines, and serve to regulate many aspects of cellular growth and differentiation.
Results:
Here, we investigate whether RGMa, RGMb, and RGMc play required roles in BMP and TGFbeta signaling in the mouse myoblast C2C12 cell line. These cells are responsive to BMPs and are frequently used to study BMP/TGFbeta signaling pathways. Using siRNA reagents to specifically knock down each RGM protein, we show that the RGM co-receptors are required for significant BMP signaling as reported by two cell-based BMP activity assays: endogenous alkaline phosphatase activity and a luciferase-based BMP reporter assay. Similar cell-based assays using a TGFbeta-induced luciferase reporter show that the RGM co-receptors are not required for TGFbeta signaling. The binding interaction of each RGM co-receptor to each of BMP2 and BMP12 is observed and quantified, and equilibrium dissociation constants in the low nanomolar range are reported.
Conclusion:
Our results demonstrate that the RGMs play a significant role in BMP signaling and reveal that these molecules cannot functionally compensate for one another.
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