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Suramin Interacts With RANK and Inhibits RANKL-induced Osteoclast Differentiation

Suramin Interacts With RANK and Inhibits RANKL-induced Osteoclast Differentiation

Ajit Regmi, Tina Fuson, Xuhao Yang, Joanne Kays, Christopher Moxham, Edward Zartler, Srinivasan Chandrashekhar, Rachelle J Sells Galvin

Bone. 2005 Feb;36(2):284-91.

PMID: 15780954

Abstract:

Suramin is a naphthalene trisulfonic acid derivative that inhibits osteoclast differentiation and bone resorption in vitro and in vivo; however, the mechanisms underlying this activity have not been studied. Receptor activator of NF-kB (RANK) ligand (RANKL) is a key regulator of osteoclast differentiation and function and this study evaluated the ability of suramin, which has been shown to disrupt protein-protein interactions, to interfere with RANKL functional activity and binding to RANK. Suramin inhibited osteoclastic bone resorption in a calvarial model and inhibited osteoclast differentiation in RANKL-stimulated murine spleen cells and RAW264.7 cells. RANKL-induced second messenger signaling (AKT and p38 MAP Kinase phosphorylation) was completely blocked by 100 microM suramin. The ability of RANKL to bind to recombinant human RANK-Fc (rhRANK-Fc) was reduced 50% by suramin in an in vitro binding assay. Surface plasmon resonance technology and nuclear magnetic resonance (NMR) were used to evaluate the ability of suramin to bind to rhRANK-Fc. Suramin was found to selectively interact with immobilized rhRANK-Fc chimera in a concentration-dependent manner by Biacore 3000 analysis. Similar results were obtained using saturation transfer difference NMR spectroscopy to demonstrate that suramin binds to rhRANK-Fc, but not IgG1Fc or sRANKL. In summary, these findings demonstrate that suramin inhibits sRANKL-induced osteoclast differentiation and suggest that these effects are mediated by suramin binding to RANK and blocking the ability of sRANKL to induce second messenger signaling.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413745	RANK/Fc Chimera from mouse			Price

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