کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9105142 | 1153406 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Suramin interacts with RANK and inhibits RANKL-induced osteoclast differentiation
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
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چکیده انگلیسی
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 μM 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 36, Issue 2, February 2005, Pages 284-291
Journal: Bone - Volume 36, Issue 2, February 2005, Pages 284-291
نویسندگان
Ajit Regmi, Tina Fuson, Xuhao Yang, Joanne Kays, Christopher Moxham, Edward Zartler, Srinivasan Chandrashekhar, Rachelle J. Sells Galvin,